Serum levels of haloperidol and reduced haloperidol as well as the reduced haloperidol/haloperidol ratios were determined in nine acute schizophrenics on oral haloperidol medication and correlated over 21 days with psycho pathology and extra-pyramidal symptom scores. We have investigated red blood cells haloperidol reductase activity in the group of patients. Significant correlations were found between haloperidol plasma levels and positive sub scale for each patient (r = 0.86 and p < 0.01; r = 0.70 and p < 0.05). We found a correlation between red blood cells reductase activity and the improvement of the psychotic anxiety scale (r = 0.64/and p < 0.05; r = 0.67 and p < 0.05), but not with reduced haloperidol/haloperidol ratios in plasma. The knowledge of reductase activity could predict the treatment response in acute schizophrenic patients. We suggest that the reported inter individual and inter ethnic differences in haloperidol and reduced haloperidol and in clinical response and adverse effects may be a reflection of genetic control of the two oxidative pathways mediated by cytochrome P450 isozyme and/or the reductase pathway mediated by haloperidol reductase in individual subject.