Background: Antisocial behavior and substance dependence disorders exact a heavy financial and human cost on society. A better understanding of the mechanisms of familial transmission for these "externalizing" disorders is necessary to better understand their etiology and to help develop intervention strategies. Objectives: To determine the extent to which the family transmission of externalizing disorders is due to a general vs a disorder-specific vulnerability and, owing to the genetically informative nature of our data, to estimate the heritable vs environmental nature of these transmission effects. Design: We used structural equation modeling to simultaneously estimate the general and specific transmission effects of 4 externalizing disorders: conduct disorder, adult antisocial behavior, alcohol dependence, and drug dependence. Setting: Participants were recruited from the community and were interviewed in a university laboratory. Participants: The sample consisted of 542 families participating in the Minnesota Twin Family Study. All families included 17-year-old twins and their biological mother and father. Main Outcome Measure: Symptom counts of conduct disorder, the adult criteria for antisocial personality disorder, alcohol dependence, and drug dependence. Results: Transmission of a general vulnerability to all the externalizing disorders accounted for most familial resemblance. This general vulnerability was highly heritable (h2=0.80). Disorder-specific vulnerabilities were also detected for conduct disorder, alcohol dependence, and drug dependence. Conclusions: The mechanism underlying the familial transmission of externalizing disorders is primarily a highly heritable general vulnerability. This general vulnerability or common risk factor should be the focus of research regarding the etiology and treatment of externalizing disorders.