The effects of elective coronary artery bypass grafting (CABG) and the associated endocrine stress response on natural killer (NK) cell activity in peripheral blood, the distribution of lymphocyte sub-populations, and the phytohemagglutinin (PHA)-induced lymphocyte transformation were studied in 20 patients anesthetized with cither etomidate-high dose fentanyl (75–125 μg · kg-1) or midazo-lam-low dose fentanyl (<20 μ · kg-1). The endocrine response to surgery was measured as changes in scrum cortisol, plasma epinephrine, and norepinephrine. Compared with control values, a significant increase of NK cell activity was found in both groups prior to induction of anesthesia, followed by a decrease after induction until initiation of cardiopulmonary bypass (CPB) and a gradual increase to levels exceeding controls during CPB. Postoperatively, NK cell activity and the lymphocyte transformation to PHA stimulation were significantly depressed for at least 1–3 days. These changes were accompanied by severe lymphopenia affecting the T-lymphocytes (T3, T4, and T8) and the NK cells (Leu 11). Apart from a delayed cortisol increase in the etomidate group, the endocrine response showed a similar pattern in the two groups. Compared with control values, a significant decrease in the serum cortisol until CPB could be demonstrated, followed by a significant increase persisting for at least 6 days postoperatively. The plasma catecholamines showed a steep rise and, consequently, a significant increase during CPB, followed by a gradual return to control values in the postoperative period. The results indicate that, in patients undergoing CABG, immune surveillance is impaired prior to CPB and during the early postoperative period. The mechanisms underlying the fluctuations in NK cell activity and lymphocyte function arc complex, but the results suggest that the endocrine stress response may be of major importance.