This study examines the prevalence of problem behaviors (sexual activity, substance use, delinquency, and school failure) in a clinical hospital-based sample of 217 inner-city, 14 to 17 year olds with a variety of serious, chronic medical illnesses and compares this prevalence to that in a group of 121 similar-aged, healthy friends with no known chronic illnesses living in the same community. No differences were found between groups in substance use, delinquency, percent who had ever had sexual intercourse, or mean age at first intercourse. There was a significant interaction effect of chronic illness and gender on age at first intercourse (p = .015); boys without chronic illness initiated sexual intercourse at a younger age than their girlfriends without illness. Contrary to expectations, significantly more of the healthy friends had repeated a grade in school than had those with chronic illness (p = .002). Results are discussed in terms of the interrelationships of chronic illness, gender, and environment on problem behaviors.