Smooth pursuit eye movements (SPEM) are often abnormal in schizophrenic patients and have been proposed as a trait marker of the disorder. We explored the use of SPEM as an outcome measure in an open-label clinical trial of famotidine, an H-2 antagonist, in patients with schizophrenia; famotidine has been proposed as an adjunctive medication, particularly for negative symptoms. Prior studies using SPEM as an outcome measure have not found a significant effect with "typical" neuroleptic medication, and one study found greater SPEM dysfunction with clozapine treatment. In this study, 19 schizophrenic subjects were stabilized for at least 1 week on conventional neuroleptic medications and then administered oral famotidine, 100 mg daily, for an additional 3 weeks. SPEM and clinical measures were assessed. Whereas Brief Psychiatric Rating Scale (BPRS) and Schedule for Assessment of Negative Symptoms (SANS) scores decreased significantly with famotidine administration, there was no significant change in SPEM performance over the course of the study. Two subjects (11%) doubled their signal/noise ratio and maintained this increase after famotidine discontinuation, whereas three subjects (17%) approximately halved this ratio and returned to baseline after famotidine discontinuation. SPEM changes were not found to correlate significantly with changes in BPRS or SANS scores. These findings suggest that SPEM dysfunction reflects a "trait" rather than clinical "state" in schizophrenia, and changes in SPEM performance might not be expected always to parallel changes in clinical ratings.