Because little data are available on the neuropsychological functioning of severely and persistently mentally ill (SPMI) persons who are homeless, our primary goal was to describe accurately and extensively the general neuropsychological functioning of a large group of such homeless individuals. In addition, we have sought to examine the relationship between some neuropsychological functions and demographic, illness, and clinical state measures in this population. A 5-hour neuropsychological test battery was administered to 116 SPMI homeless individuals. Neuropsychological, diagnostic, substance abuse, clinical, and psychopathology data were obtained in a standardized manner. SPMI homeless individuals were significantly impaired on a wide range of neuropsychological functions. Specific test performances were most significantly related to precursor variables (level of education and parental socioeconomic status) and state variables (level of psychosis and anticholinergic medication dose). Gender and substance abuse had significant effects limited to sustained attention. Neuropsychological performance was impaired in this sample of homeless SPMI persons. Further research, using profile analysis to directly compare groups composed of homeless persons without psychiatric illness or demographically matched persons of comparable psychiatric status who are not homeless will help clarify the role of homelessness and psychosis on neuropsychological function.