Previous research has found that both schizophrenics and their relatives have significantly elevated rates of clinical neurologic signs--including 'hard' signs screened to exclude artifacts. The present study examined whether hard signs that indicate relatively localized dysfunction in particular brain regions significantly distinguish schizophrenics and/or their non-schizophrenic relatives from psychiatrically normal controls and patients with other disorders. All patients were diagnosed with DSM-III or DSM-IIIR criteria, using information from structured interviews, supplemented by chart review and family informants. Subjects were administered clinical neurologic examinations by a neurologist blind to diagnosis. The proband sample, composed of 54 schizophrenic or schizoaffective subjects, had a significantly greater proportion of subjects with signs of cerebellar dysfunction than any of the comparison samples, which included: 44 control subjects, 24 patients with substance abuse, 37 patients with bipolar disorder, and 73 of the probands' non-schizophrenic parents and adult siblings. Proportions of both probands and their relatives with signs of dysfunction of sensory cortex were significantly higher than for other groups. Cerebellar and sensory cortical dysfunctions may distinguish different subgroups of schizophrenics and may tend to reflect, respectively, non-familial and familial neuropathological factors.