The effect of 2,450 MHz CW microwaves on natural killer (NK) cell activity and lymphocyte responsiveness to mitogen stimulation was studied in mice. Groups of mice were irradiated at power densities of 5, 15, or 30 mW/sq. cm. (SAR =3.5, 10.5, and 21 W/kg respectively) for 1.5 h on 2 or 9 consecutive days. NK cell activity was determined using an in vitro51 Cr release cytotoxicity assay and an in vivo tumor-cell clearance assay. No consistent change was observed in the mitogen response of spleen cells from sham compared with irradiated mice. A significant suppression of NK cell activity measured in vitro was observed for mice irradiated at 30 mW/sq. cm., but not at 15 or 5 mW/sq. cm. A significant suppression of NK cell activity, as determined using the in vivo tumor clearnance assay, was also observed at 30 mW/sq. cm. NK cell activity, as determined using the in vivo assay, returned to normal within 24 h following the last irradiation. Treatment of mice with hydrocortisone caused suppression of NK cell activity measured in vitro and in vivo.