Subjective effects of marijuana and cocaine use are associated with amount of drug use and potentially with risk of abuse and dependence. We used Latent Class Analyses (LCA) to examine subjective responses to two categories of drugs and link these to abuse and dependence. In 1992, subjective responses were queried of 2506 marijuana and 661 cocaine lifetime users who were members of the Vietnam Era Twin Registry. LCA was used to identify classes of subjective effects. Multinomial logistic regression models were computed to test for an association between classes and marijuana and cocaine abuse or dependence. The best LCA solution for marijuana identified 6 distinct classes characterized as positive, relaxed, reactive, adverse, low and very reactive. The best LCA solution for cocaine identified 5 distinct classes characterized as positive, alert, adverse, low and very reactive. Marijuana abuse and dependence were significantly associated with each latent class. Cocaine abuse was associated with the reactive class (OR=3.9; 95% CI: 1.6-9.5). Cocaine dependence was associated with reactive (OR=15.3; 95% CI: 7.1-32.6), adverse (OR=9.7; 95% CI: 4.5-21.0) and very reactive (OR=18.7; 95% CI: 5.6-62.6) classes. We found evidence for both qualitative and quantitative subjective effect profiles. Subjective effects, both positive and adverse are associated with lifetime risk for marijuana and cocaine dependence.