Male C57 mice kept under a 14:10 (L:D) photoperiod received vehicle (VEH), melatonin (MEL) and methoxytryptamine (MTA) in the drinking water for 2 weeks. Splenocytes from MEL-treated mice showed an augmented mitogenic response to concanavalin A and lipopolysaccharide (LPS) while splenocytes from MTA-treated mice demonstrated an enhanced mitogenic response to LPS when compared to the VEH-treated control. Splenocytes from MEL-treated and MTA-treated mice also produced higher levels of gamma interferon and interleukin-2. Lymphokines prepared from splenocytes of MEL-treated mice stimulated peritoneal macrophages to produce more nitrite than those from splenocytes of MTA-treated and control mice, suggesting that MEL had a stronger stimulating effect on the lymphocytes than MTA. Understimulation of lymphokines from MEL-treated mice, peritoneal macrophages from MTA-treated mice produced a greater inhibition of the growth of murine mastocytoma P815 cells than that produced by macrophages from control and MEL-treated mice, suggesting that MTA was more potent than MEL in rendering the macrophages responsive to lymphokines. The results point to immunostimulatory actions of the pineal indoles MEL and MTA.