BACKGROUND Serotonin (5-HT) regulates hypothalamic-pituitary-adrenal (HPA) axis activity. Abnormal response to the dexamethasone suppression test (DST) and altered platelet 5-HT concentration have been shown in some schizophrenic patients. METHODS Platelet 5-HT and plasma cortisol concentrations were determined simultaneously in 86 male schizophrenic patients before and after DST. Basal plasma cortisol and platelet 5-HT levels were also determined in 69 healthy male persons. RESULTS Schizophrenic patients had higher plasma cortisol and platelet 5-HT concentrations than healthy persons. An abnormal escape from dexamethasone suppression was observed in 50% of patients. In these patients predexamethasone cortisol and platelet 5-HT concentrations were higher than in patients with normal DST. CONCLUSIONS This study demonstrates that schizophrenic patients have the HPA axis dysregulation that could be connected with a disturbance in the 5-HT system.