The relationship between plasma prolactin (PRL) and drug levels in patients receiving neuroleptic drugs is of special interest in view of evidence that the PRL elevation induced by these drugs reaches its maximum at sub-therapeutic doses. Plasma PRL and fluphenazine (FPZ) levels were measured by radioimmunoassay (RIA) in each of 11 chronic schizophrenics (nine men, two women) during two 4-week periods of treatment with FPZ enanthate at a "High Dose' (250 mg per week) and a "Low Dose' (12.5 mg per week) given in random order. Plasma PRL levels were above normal in 9 of 11 subjects during the last week of Low Dosage. High Dosage resulted in PRL levels significantly greater than found during Low Dose treatment in 9 of 11 patients. Thus the PRL response had not reached its "ceiling" during Low Dosage in most patients. A significant correlation between PRL and FPZ levels was found in seven subjects; evidence that immunoreactive FPZ levels relate to an effect caused by blockade of dopamine receptors. The plasma FPZ pattern between injections during week 1 of Low Dosage was remarkably stable; High Doses produced an initial drug peak at 1--2 h and a secondary peak occurring on days 2--3 followed by a return to preinjection levels by day 7.