In the present study we evaluated the ability of either medroxyprogesterone acetate (MPA) or megestrol acetate (MA) to reduce cisplatin (CDDP)-induced serotonin (5-HT) release from peripheral blood mononuclear cells (PBMC) of cancer patients. Sixteen patients with cancer of different sites, all in advanced stage of disease, were studied (10 for MPA and 6 for MA). The levels of 5-HT in culture supernatants of PBMC stimulated with CDDP were higher than controls (100 nM vs 51 for MPA study and 123 vs 64 for MA study) and were in the same range of PHA-stimulated PBMC. The addition into cultures of MPA or MA was able to significantly reduce the CDDP-induced production of 5-HT (62 nM for MPA, and 46 for MA study). MPA as well as MA are able to inhibit 5-HT production and/or release by CDDP-stimulated PBMC of cancer patients: this finding to our knowledge has not been previously reported. The concentrations of MPA and MA used in cultures were in the same range as those raised in plasma following the clinical administration of daily doses of 1,000/2,000 mg of MPA and 320 to 960 mg of MA.