Data ascertained in a study of club drug use among 450 gay and bisexual men indicate that at least one class of PDE-5 (phosphodiesterase type 5 inhibitor, sildenafil [Viagra]) is used frequently in combination with club drugs such as methamphetamine, MDMA (3,4 methylenedioxymethamphetamine [ecstasy]), ketamine, cocaine, and GHB (gamma hydroxy butyrate). Patterns of sildenafil use in combination with each of the club drugs differ among key demographics including race and age. Multivariate models, controlling for demographic factors, suggest that contextual factors are key to understanding why men mix sildenafil with club drugs, although age may still be an important issue to consider. Of particular importance is the fact that use of club drugs in combination with sildenafil is strongly associated with circuit and sex parties, where a centerpiece of these environments focuses on sexual exchange. These models imply interplay between person-level and contextual factors in explaining drug use patterns and further indicate that interventions aimed at addressing illicit substance use must carefully consider the role of environmental factors in explaining behavior.