NK cell activity declines with age and is strain dependent. We investigated the age associated decline of NK cell activity in the HW26C strain of mice. The bilineal congenic strain HW26C which contains a segment of chromosome 4 of BALB/cBy introduced onto the C57BL/6By (B6) background was used to investigate the decline of NK cell activity with age. Our experiments showed that there is a significant decline of NK cell activity in old (18-26 months) HW26C mice as compared to the B6. By contrast, the NK cell frequency determined using a surface marker for NK cells, NK1. 1, did not show any significant difference with age. It appears therefore, that the decline in NK activity during aging is a reflection of loss of lytic activity rather than an actual decline in the number of NK cells and the responsible gene (s) resides in chromosome 4.