Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of hypothalamic-pituitary-adrenal axis (HPA) activity and prolactin (PRL) secretion. The present study examined the relationship between platelet 5-HT and plasma cortisol and PRL concentrations in 20 schizophrenic, 25 depressed, and 25 healthy women. At the time of blood sampling, the schizophrenic and depressed patients had been drug-free for at least 7 days. Platelet 5-HT, plasma cortisol and PRL concentrations were determined by spectrofluorimetric, radioimmunoassay and immunoradiometric methods, respectively. Platelet 5-HT concentration was significantly higher in schizophrenic patients than in depressed patients or in healthy controls, while it was significantly lower in depressed patients than in healthy controls or in schizophrenic patients. Plasma cortisol levels were significantly increased both in schizophrenic and in depressed patients compared with values in healthy controls. Values of plasma PRL were similar across groups. A significant correlation was found between platelet 5-HT and plasma cortisol, and platelet 5-HT and plasma PRL concentrations in healthy controls, but not in schizophrenic or depressed patients. There was no significant relationship between plasma PRL and cortisol levels in any of the groups. Our data, although obtained on peripheral biochemical markers, indicate that depression and schizophrenia are characterized by disturbed 5-HT transmission and dysregulated HPA axis activity.