Monocytes, recovered from human peripheral blood by counter-current centrifugal elutriation (CCE), suppressed baseline natural killer (NK) cell cytotoxicity (NKCC) and rendered NK cells resistant to activation of cytotoxicity by human recombinant interferon-alpha (IFN-alpha) by a cell contact-dependent mechanism. Monocyte-induced suppression of resting and IFN-activated NK cells was abrogated by the biogenic amines histamine [via H2-type receptors (H2R)] and serotonin [via 5-HT1A-type receptors (5-HT1AR)]. Our data are suggestive of a monocyte/NK cell interaction that is subject to regulation by biogenic amines.