Alternative high school (AHS) students typically report higher levels of alcohol and other drug use compared to students attending traditional high schools. Greater use of such drugs as heroin, methamphetamines, and cocaine in this at-risk population may be driven, in part, by a greater latitude of acceptance toward substance use in general, which may accelerate the transition from gateway drugs to hard drugs. Seven hundred seventy-seven adolescents (mean age 16.6; 56% female) were recruited from alternative high schools throughout Southern California. To understand the factors that may lead AHS students to use hard drugs, a model was tested in order to determine if AHS students' latitude of acceptance toward substance use was a mediator between the relationship of past use of gateway drugs and future use of hard drugs. Latitude of acceptance was found to be a statistically significant mediator of future hard drug use (b = 0.03, 95% confidence intervals = 0.01 to 0.05) among gateway drug users. An individual's latitude of acceptance to various drug use behaviors may be consistent with societal norms. However, after exposure to, or use of, gateway drugs, attitudes that are more permissive toward hard drug use may be encountered, the acceptance of hard drugs may expand, and the use of hard drugs may escalate. Interventions designed to reduce the use of hard drugs among at-risk youth may be more persuasive by crafting messages that are within the latitude of acceptance of the target population and prevent the acceptance of hard drug use.