Differences between 24 female and 35 male clients were assessed at entry into an intensive case management program serving homeless shelter residents and again nine months later. Both men and women were socially isolated, with small social networks and severe deficits in social functioning. Histories of homelessness were similar for both genders, and there were no gender differences in psychopathology at baseline or follow-up. At entry into the program women had higher levels of social skills, larger and more supportive networks, and better housing conditions than men, but these differences disappeared after the subjects spent nine months in the program. Inadequate living conditions may have contributed to the more negative initial picture for men. Although there were more similarities than differences between the men and women in this sample, more research on gender differences is needed to design and evaluate programs for homeless mentally ill persons.