OBJECTIVE: This is the first study investigating physical aggression toward others and toward self (self-injurious behavior [SIB]) and its association with comorbid disorders and symptoms and demographics in large autism, ADHD, and population-based samples. METHOD: The referred sample comprised 2,456 children (1,415 with autism, 739 with ADHD-combined, and 302 with ADHD-inattentive) aged 2 to 17 years. The population-based sample consisted of 665 children evaluated at baseline (6-12 years of age) and 259 reevaluated at follow-up (12-17 years). The Pediatric Behavior Scale was rated by mothers yielding scores on 2 dependent variables: physical aggression ("hits, bites, or throws things at people") and SIB ("bites or hits self, bangs head, or repeats other acts causing self-injury") and 9 independent variables (oppositional behavior, irritability, conduct problems, hyperactivity, impulsivity, autism, inattention, anxiety, and depression). RESULTS: Physical aggression was strongly linked with the autism and ADHD-combined groups (28% and 20% often a problem) but not the ADHD-inattentive or community group (2%). SIB was primarily associated with autism (16% often a problem). Irritability, conduct problems, and younger age were significant concurrent predictors of physical aggression in most groups, and irritability predicted SIB in autism and ADHD-combined. IQ, sex, race, and parent occupation were not predictors. CONCLUSION: Physical aggression is common in autism and ADHD-combined, whereas SIB is strongly linked with autism. The irritability component of oppositional defiant disorder and not oppositional behavior significantly predicted physical aggression and SIB. In addition to treating aggression directly, addressing irritability with the use of pharmacological, behavioral, and psychosocial interventions may also decrease aggression.