Serotonin inhibited in a concentration dependent way (10⁻³ M to 10⁻¹⁰M) the LPS induced Tumor Necrosis Factor-α synthesis both, when added to the monocyte cultures from the beginning and when added together with the activating stimulus 8 hours before the end of the culture. The inhibitory effect was specifically blocked by the 5-HT₁ and 5-HT₂ serotonin antagonist methysergide and the 5-HT₂ receptor antagonist ketanserin. This indicates that only the 5-HT₂ receptor family (5-HT₂ or 5-HT_1C) may be involved in the inhibitory effect. Serotonin seems to play an important immunomodulatory role in macrophage functions.