Background: Some studies of premenopausal women suggest that the severity of psychopathology associated with schizophrenia may be related to levels of estrogen. Methods: We examined psychopathology in community-dwelling postmenopausal women with schizophrenia who had received ( n = 24) versus had never received ( n = 28) hormone replacement therapy. Results: Users of hormone replacement therapy and nonusers did not differ significantly with respect to age, ethnicity, education, age of onset, duration of schizophrenia, global cognitive functioning, or neuroleptic-induced movement disorders. The hormone replacement therapy users received lower average daily doses of antipsychotic medication; they had similar levels of positive symptoms but significantly less severe negative symptoms compared with hormone replacement therapy nonusers, independent of differences in antipsychotic dosage. Conclusions: Our results suggest that the use of hormone replacement therapy in conjunction with antipsychotic medication in postmenopausal women with schizophrenia may help reduce negative, but not positive, symptoms.