Findings from the study suggest several things about gender, strain, and deviance. First, males and females respond differently to similar types of strain, with males relying on deviant coping more than females. Second, females tend to vary more than males in their reactions to strain, responding to cumulative strains with despair and negative parental reactions to dropout with drug use. The results also suggest that substantive differences exist in the types of stressful events the genders mitigate with drug use. Specifically, negative parental reactions as well as the social bonds index had statistically significant effects on female but not male drug use. Despite this study’s strong and unwavering support for the strain-negative emotion portion of General Strain Theory (GST), negative emotions, such as despair, did in turn significantly increase drug use, a finding consistent with the GST. Dropping out of high school is generally considered to be a negative life event for youth. They can have a greater prevalence of both licit and illicit substance use. The study considered a more inclusive conceptualization of strain to explain deviance among high school dropouts by applying a newer version of the theory, General Strain Theory (GST) to study the problem. It argues that strain is generated by more general processes, such as the failure to achieve positively valued goals, the removal or threatened removal of positively valued stimuli and/or the presentation or threatened presentation of negative stimuli. GST argues that drug use is one way adolescents mitigate negative emotions brought on by aversive environmental stimuli. This study tested the mediating effects of despair on the strain-drug use relationship, evaluating the effects of parental reactions to leaving school on post-dropout drug use. Tables, appendix and references