Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment.