The presence of mental disorder and cognitive functioning were examined in groups of 20 multiple sclerosis (MS) and homosexual acquired immunodeficiency syndrome (AIDS) ambulatory male outpatients matched for disability and demographic features. Patients who were somatically ill, had past central nervous system infection or tumours or abused intravenous drugs or alcohol were excluded. The groups significantly differed in mental symptoms and mental disorders (DSM-III classification) seen currently and after the diagnosis of MS or human immunodeficiency virus-1 infection. AIDS patients had pre-existing anxiety disorders that affected their current mental symptoms. MS patients showed more evidence of cognitive impairment than equally disabled AIDS patients. The differing neural and mental features are discussed in relation to the current concepts of subcortical and cortical disorders.