Thirty schizophrenic patients received intravenous dextro-amphetamine while on and off pimozide. The results provide evidence that negative symptoms and depressed mood in schizophrenia respond in part to intravenous challenges of dextro-amphetamine. Improvement in negative symptoms while on d-amphetamine correlated significantly with subsequent improvement in the same negative symptoms while on pimozide. These results do not support the Type II model of irreversible negative symptoms in schizophrenia in our patient sample. Changes in negative symptoms may be related to state dependent changes in the dopamine system, but noradrenergic mechanisms cannot be excluded either.