A study of inner-city Black and Caucasian males and females in two junior and two senior high schools provided data on sexual knowledge, attitudes and behaviors, and substance use based on over 2500 anonymous, voluntary self-administered questionnaires. Substance use was high among Caucasians, particularly females. Females smoked more cigarettes than males and men drank more alcohol. Marijuana smoking showed only small racial, age, and gender differences. Compared to Blacks, Caucasians used more hard drugs. Using an index scoring types of substances and frequencies of use, sexually active students were higher than virgins in all subgroups, with those who initiated intercourse early appearing highest on the index. A regression model explaining 21% of the variance in substance use showed independent effects of age, race, gender, and sexual activity. The importance of an index for screening early use is discussed, and research on the relationship of low-level youthful experimentation with future dysfunctional use is proposed.