The results of two epidemiological studies suggest a hereditary predisposition to develop drug-induced parkinsonism. We investigated human leukocyte antigen (HLA) antigen prevalence rates in patients with neuroleptic-induced parkinsonism. Fifty-two male, white, neuroleptic-treated, chronic in-patients with DSM-III-diagnosed schizophrenia were examined for the presence of parkinsonism. Subjects were tested for 23 type A, 43 type B, 4 type C, and 10 type DR HLA antigens. The group of schizophrenic patients with parkinsonism (n = 29) was compared with the group of schizophrenic patients without parkinsonism (n = 23). There were no significant differences between the two groups with respect to age, duration of neuroleptic exposure, or anticholinergic drug exposure. One HLA antigen, B44, was significantly more prevalent in the group with parkinsonism than in the group without parkinsonism. We derived a relative risk of 7.16 for drug-induced parkinsonism with HLA-B44 present in this group of schizophrenic patients. These data indicate that HLA-B44 may play a role in genetic or immunologic susceptibility to develop drug-induced parkinsonism in white schizophrenic individuals.