The primary hypothesis of this study was that females would report greater incidence of symptoms of physical dependence, and/or report them at a younger age. Also tested was whether the females would progress faster to regular substance use and whether the incidence of specific psychiatric diagnoses was similar across genders. One hundred adolescent inpatients (42 percent female) seeking treatment for a substance use disorder (SUD) were assessed with the Comprehensive Addiction Severity Index (C-ASI) and other standardized assessment instruments. The psychiatric variables included age of first use, progression to regular use, endorsement of dependence symptoms, psychiatric diagnoses, and family functioning. The findings indicate that male and female adolescents with SUD differed on whether and when they experienced physical symptoms of dependence. Females were more likely to endorse dependence symptoms and report experiencing symptoms at a younger age, despite the fact that the genders did not differ on frequency of use. Genders differed in the number of substances used. Females were faster to progress from first use to regular use for both alcohol and marijuana. They progressed to regular use of these drugs in about half the time as the males. Few gender differences were found in the rates of psychiatric diagnoses. The results of this study add to the growing evidence that male and female adolescents with SUD differ in their clinical presentation. Females may be particularly vulnerable to or may be greater endorsers of substance dependence symptoms. Future studies should investigate the physiologic and psychologic basis of this increased sensitivity in females and their faster progression to regular substance use. 2 figures, 3 tables, 30 references