Levels of haloperidol were determined by radioimmunoassay (RIA) in 30 schizophrenic patients (diagnosed according to the criteria of DSM-III), who were treated with fixed doses of this neuroleptic for a period of 21 days. An inverted U-shaped relationship was found between the percent improvement observed in the BPRS global score and the steady state of haloperidol. The interval of effective concentration of haloperidol was set between 12.0 and 35.5 ng/ml. However, the limits of such an interval found in the subchronic schizophrenic subgroup (SS) ranged from 7.4 to 24.9 ng/ml, whereas in the chronic schizophrenic subgroup (CS), it ranged from 14.8 to 38.5 ng/ml. This finding suggests that the interval of effective concentrations may vary as a function of the number of years of evolution of the subjects' illness. This may be compatible with the development of tolerance in the mesolimbic and/or mesocortical dopaminergic systems as a response to prolonged neuroleptic treatments.