This study was aimed at evaluating the effect of histamine on tumor necrosis factor (TNFα) secretion by purified human blood monocytes. TNFα was measured by radioimmunoassay. Histamine caused a dose-dependent inhibition of lipopolysaccharide-induced TNFα production from human blood monocytes, averaging maximally 50% at 10––5M. Preincubation of mononuclear cells with an H2 antagonist (cimetidine), but not with an H1 antagonist (promethazine) prevented this inhibitory effect of histamine. In conclusion, histamine causes, in vitro, a depression of TNFα secretion by human monocytes through activation of H2 receptors.