Natural killer (NK) cell function in relation to immunophenotypical signs of NK activation was studied prospectively in 15 renal transplant patients with cytomegalovirus (CMV) infection. NK activity (expressed as the percentage of K562 lysis) before onset of CMV infection reached a median of 6% (range 2-18%), comparable to values observed in noninfected controls [7% (range 7-21%), P < .1]. During CMV infection, NK activity rose to a maximum of 25% (6-60%) (P < .001 vs. controls). Maximal values exceeded the upper level of controls in nine of 15 patients. NK activity was correlated to the number of CD56+HLADR+ cells in the peripheral blood (r = .57, P < .001). These data suggest that NK cells play a role in the recovery from CMV infection in a substantial number of patients and that immunophenotypical analysis of NK activation provides a surrogate marker of NK cell function.