Muramyl peptides (MPs) are regulators of macrophage function. That the activities of MPs may be mediated by serotonin (5-HT) is supported by earlier work that demonstrated specific binding sites for MPs on macrophages that competitively bind 5-HT. Both mediators were also shown to enhance the production of superoxide anion (an antibacterial agent) by these cells. We now report on two additional macrophage activation phenomena affected by 5-HT: phagocytosis and induction of tumor necrosis factor alpha (TNF) mRNA. Serotonin acts as a muramyl peptide-like agonist by increasing phagocytosis of tubercle bacilli by murine peritoneal macrophages, and as a partial agonist/antagonist in the induction of mRNA for tumor necrosis factor. These observations provide further evidence for a serotonergic involvement in some of the physiological responses to MPs.