Double-blind haloperidol was administered during two consecutive 3-week periods to 65 patients with acutely exacerbating schizophrenia or schizoaffective disorder. Two plasma levels were targeted. low (2 ng/mL) and moderate (10 ng/mL). The subjects were randomly assigned to four treatment sequences (low-low, low-moderate, moderate-moderate, or moderate-low). Data from 28 patients were available for the analyses of the second study period. In that period, decrease of plasma levels reduced mild but not severe negative symptoms. Thus, lowering of the plasma levels after the first 3 weeks of treatment may improve mild negative symptoms. Conversely, increasing the plasma levels may make mild negative symptoms worse.