Summary: The usefulness of the histamine-2 (H2) antagonist famotidine as an adjunct to conventional antipsychotic treatments of idiopathic psychotic disorders (i.e., schizophrenia and schizoaffective disorder) was investigated in an open-label study. After stabilization for at least 1 week with their conventional antipsychotic medication regimen, 10 patients completed a 3-week study period in which famotidine (20 mg twice a day) was added as an adjunctive medication. The 10 patients were all somewhat treatment refractory and had spent a mean of 230 days of the previous 2 years in the hospital. Total Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression scores were significantly lower during the 3 weeks with famotidine compared with the week before and after its administration. Nevertheless, review of the scores revealed that the magnitude of the changes were small. Negative symptoms as measured by the Schedule for the Assessment of Negative Symptoms (SANS) were not significantly different during famotidine treatment, although there was the tendency for total SANS scores to be lower during famotidine treatment. When BPRS items were divided into specific versus nonspecific symptom subscales, only the specific-item subscales had significantly improved during famotidine treatment. The results of this study suggest that famotidine might prove a useful adjunctive agent in certain patients with schizophrenia. Future studies using a double-blind placebo-controlled design and higher doses are needed. Additionally, other H2 receptor antagonists with better penetration across the blood-brain barrier should be pursued.