Longitudinal data from 746 virgins (310 males) aged 12 to 16 years were analyzed to assess the relationship between baseline substance use and sexual initiation 3, 6, and 9 months later. Compared to virgins with no substance use, virgins who had used three or more substances were three times more likely to initiate sex over the ensuing 9 months. The use of alcohol, tobacco, and marijuana and the use of more than three substances are highly specific for predicting sexual initiation.