Treatment of neonatal female mice with DES markedly reduced the activity of NK cells in adult mice. This finding was most evident in C57BL/6 and BALB/c strains, but was also found in outbred NMRI mice. The mechanisms behind the reduced NK activity was further analyzed. No evidence of DES-induced cellular or humoral suppressors of natural killing could be detected. Pregnancy was found to be without effects on NK. Poly I:C augmented the NK activity in control females but even very high doses of Poly I:C failed to increase the level of NK activity in neonatally DES-treated animals. The lack of response to boosting with Poly I:C was not due to alterations in kinetics of NK induction.