Phytohemagglutinin (PHA) was capable of inducing non‐cytotoxic histamine release from human leucocytes. In the presence of deuterium oxide (D2O), PHA caused significantly greater histamine release. Dibutyryl cyclic AMP id‐cAMP) could enhance the histamine release in the presence of D2O although it was an inhibitor of the release if used alone. However, a β agonist, isoproterenol, which increases intracellular level of cAMP was inhibitory with or without D2O. These data ask the question about dual effect of cAMP and suggest the possibility of different pools of cAMP in the target cells.