Natural killer (NK) cell activity was evaluated in three groups of Macaca nemestrina that varied with respect to SAIDS D retrovirus serotype 2 (SRV-2Iw) and viremic status. Target cells used were Raji and K562 cells. No significant differences (ANOVA) in mean NK activity were detected among the three groups of animals studied. Using Raji targets, mean LU3,/106 ? SEM was 6.3 2 1.6 for seronegative (V-Ab-) animals, 7.3 2 1.5 for seropositive (V-Ab + animals, and 10.2 2 3.5 for persistently viremic (V+ Ab-) animals. Using K562 targets, mean LU3,/106 was 7.6 & 1.7 for seronegative (V-Ab-) animals, 6.5 & 2.5 for seropositive (V-Ab +) animals, and 5.1 & 1.9 for persistently viremic (V+Ab-) animals. Percentage blood CD16+ and CD8+ cells also were not different in the three groups of animals. NK activity did not always correlate with percentage of CD16+ or CD8' cells in peripheral blood a t the time the assays were done. In persistently viremic animals, there was a strong positive correlation between percent CD16+ and CD8+ cells and NK activity using K562 cells but not Raji cells. Depletion experiments indicated that lysis was mediated by both CD8+ and CD16+ cells with both Raji and K562 cells. However, Raji targets were a better indicator of killing mediated by CD16' cells. Our studies indicate that M. nemestrina may be classified as high or low responders with regard to NK activity, and there was no correlation with SRV-2lW viral or antibody status. Additionally, our results suggested that group housing of M. nemestrina was usually associated with increased NK activity. In conclusion, studies of NK activity in M . nemestrina should consider target cells used, phenotype of effectors, endogenous (high or low) levels of NK activity in individual animals, and housing conditions.