Acute behavioral changes following a 20 mg i.v. d-amphetamine predicted the small antipsychotic and antidepressant effects of the third week of lithium treatment in schizophrenic patients. Multivariate regression models accounted for 95% of the variance predicting the antipsychotic effects and for 89% of the variance predicting the antidepressant effects in postpsychotic depressed patients. The greater the increases in the d-amphetamine-induced changes in the thought disorder cluster of the Brief Psychiatric Rating Scale, the greater the antipsychotic effects of lithium. The data suggest that the modest behavioral changes observed with lithium in schizophrenia are most likely drug-induced.