The girls convince Johnny to invite Gil over for a sleepover.//Johnny's got a wart and it plans on sticking around! .
Johnny is part of the Test family, which consists of his 13-year-old genius twin sisters, Susan and Mary, and his over-the-top parents, his mother Lila, who is a full-blown workaholic businesswoman and his father Hugh, who is an obsessive-compulsive househusband whose two biggest obsessions are cleaning and cooking meatloaf. The Test Twins frequently use Johnny as a guinea pig for their various experiments and inventions in their laboratory filled with highly advanced technology built in over the Tests' household attic, with most of which they try to impress their pretty boy next-door neighbor, Gil, for whom both harbor a deep love and obsession, although their attempts to come up with some way to attract his attention usually end in failure.
Johnny is the troublesome and highly mischievous boy who causes a lot of problems in the family and often within the city. He is best friends with his anthropomorphic talking pet dog, Dukey, who Susan and Mary gave human-level intelligence and the ability to speak in an experiment. Because Johnny has Susan, Mary and Dukey by his side, he can live any kid's dream, only to find that most dreams never turn out as hoped. He is very hyperactive and often messes with his sisters' inventions, causing trouble and mayhem, but just as often proves himself to be extremely clever such as by frequently tricking his genius sisters or saving the day from whatever danger happens to show up. Johnny can be considered very spoiled and stubborn, as he gets what he wants through deceit, blackmail, or manipulation. However, he does have a sense of justice and tends to learn from his mistakes. He also feels remorse for any of his actions that may have hurt peoples' feelings. Johnny cares a lot about his family and has said on more than one occasion that he loves them. Johnny, like most kids despises school and goes to great lengths to avoid doing work, often using his sisters' inventions to do so and often putting himself and/or others in trouble as a result.
Though Susan and Mary generally refuse to help Johnny in his antics, they generally end up doing so anyway due to Johnny blackmailing or manipulating them, or in exchange for Johnny allowing them to use him as their aforementioned lab rat. Their sibling relationship is complicated as Johnny does risk his life to save his sisters if they are in danger. Yet they often have typical sibling arguments that sometimes grow into full on battles.
Dukey sometimes dresses as a human being when going out in public, usually in a shirt marked 'NOT A DOG', and he is addressed by others as Johnny's "hairy friend" or "the kid with the rare hair disorder" because the minor characters' lack of intellect causes them to believe that Dukey is a human. In later episodes, when Dukey is not dressed like a human and someone hears Dukey say something, they will ask "Did that dog just talk?", to which Johnny quickly replies, "No, you're just hallucinating."
One of Johnny's main nemeses is Eugene "Bling-Bling Boy" Hamilton, a fellow arch-rival of the Test sisters and frienemy of Johnny and Dukey, who acts as one of the recurring evil forces at work. He has a big crush on Susan, who does not reciprocate his feelings and generally shows no interest in him. Since season 3, Johnny has also gained a second major rival, Dark Vegan, a space warlord from the planet Vegandon, of which he is leader. Sissy Blakely is a tomboy who often serves as Johnny's rival/friend, as the two are believed to have crushes on each other, but each would instantly deny it, and they also constantly compete against each other. Sissy also has a pink laberdoodle named Missy, who is also Dukey's rival and crush. Bumper is the school bully who constantly picks on Johnny. Meanwhile, the General from the army base Area 51.1 and Mr. Black and Mr. White who are two Federal agents from the Super Secret Government Agency (SSGA) sometimes help, distract, and/or annoy the Tests on various occasions. The General and the Agents are shown to be close friends with the kids and often get them out of trouble or recruit them for an assignment. Susan also revealed to Johnny that the entire agency can be summoned by saying the secret password; "for the love of fiddlesticks!"
Johnny's catchphrase is "Didn't see that coming" during an unexpected event. There have been minor alterations to the phrase and in some cases others have said it. Meanwhile, the twins have a habit of speaking in unison, especially when reciting their catchphrase, "We're such geniuses." Other recurring catchphrases include; "Say wha...?!", "To the lab!" and most recently "That was convenient," when some mistake of Johnny's turns out in his favor. Along with an ending tagline of, "Oh, so close!" said in unison by the Test siblings and Dukey whenever they have been caught disobeying the Test parents.