The study tested whether self-discrepancy theory could account for changes in natural killer (NK) cell activity after exposure to self-referential stimuli. Anxious, dysphoric, and control Ss were pretested and 1 month later covertly exposed to their own self-guides as well as those of another S. Blood samples were drawn for analysis of NK cytotoxicity and cortisol. The dysphoric Ss manifested the greatest actual: ideal discrepancy, whereas the anxious Ss manifested the greatest actual: ought discrepancy. Content analysis of written responses showed that activating discrepancies induced specific negative states; priming discrepancies also increased cortisol for the anxious Ss. NK activity was lower after self-referential priming for both distressed groups, particularly the anxious Ss. The control Ss showed a trend toward increased NK activity after self-referential priming. The study represents the 1st experimental demonstration that negative self-evaluation can alter immune responses.