A dose-finding study of proglumide added to neuroleptics for the treatment of schizophrenic patients who were relatively refractory to their ongoing neuroleptic regimen was performed. Initially, four patients were open-label treated using a regimen of progressively increasing doses (proglumide 0.5–1024 mg/day) for 4 weeks. Afterwards, seven patients were given low doses (0.5 mg/day) followed by higher doses (500 mg/day) for a total period of 8 weeks. Overall, no improvement was seen in these refractory patients as a group at any dose. In individual patients, modest improvement or worsening of psychotic symptoms was observed. The results suggest that more potent cholecystokinin (CCK) antagonists and a greater knowledge of CCK pharmacology are needed before novel treatments exploiting the interaction of CCK and dopamine in the brain can be developed.