Data are presented on substance abuse, mental health problems, and the psychosocial well-being of 100 post-adolescents residing in a short-term shelter in south Florida. The sample was found to have high levels of social dysfunctions, e.g., low educational achievement, few job skills, poor work histories, and limited interpersonal coping networks. The Diagnostic Interview Schedule (DIS) was employed to make DSM-III diagnoses for alcohol and drug abuse, depression, and schizophrenia for three prevalence periods: ever in lifetime, past year, and past month. Overall, the sample had much higher prevalence rates for each of these disorders than those found among comparable age groups in the general population. The past month DSM-III rates were: alcohol abuse/dependence, 27.3%; drug abuse, 27.2%; major depressive episode, 20.3%; schizophrenia, 7.1%. Co-morbidity of diagnosed disorders was pervasive. Only 31% of the sample had no DSM-III diagnosis. And, of the 69% who met the DSM-III criteria for any diagnosis, all but one of them had at least one additional diagnosis as well. The personal, social, substance abuse, and mental health problems manifested by those in the sample will require major efforts to integrate them into the mainstream of American life.