PGE2 solubilized in human serum as well as dialyzed or heat inactivated human serum was tested for modulating natural cytotoxicity as compared to PGE2 solubilized in culture medium. PGE2 dissolved in human serum failed to affect cytotoxicity, while that solubilized in dialyzed or heat inactivated serum suppressed in vitro cytotoxic activity of the lymphocytes similarly to PGE2 in culture medium. It is concluded that the immunomodulatory potential of PGE2 observed in vitro is inhibited by high concentrations of human serum and that in vitro findings with this compound might not reflect the situation in vivo.