This study examined neuropsychological functioning in two subgroups of patients with familial schizophrenia. Those who showed evidence of progressive ventricular enlargement observed across serial MRI scans (n =6) were compared with subjects whose ventricular volume remained static (n =10) over an average of 28 months. No differences were found in terms of age, education, ethnicity, level of psychotic symptomatology, DSM-IV subtype, age of onset, or duration of illness. Neurocognitively, the static ventricle group was impaired across more cognitive domains and had a larger percentage of subjects falling into the impaired range on a majority of measures, with the greatest differences on measures of attention (p <0.02) and nonverbal memory (p <0.07). These results suggest that clinically meaningful differences between these two MRI-derived subgroups of patients with schizophrenia may exist, and further underscore the heterogeneity of the illness.