Interleukin-6 (IL-6) and alpha-melanocyte-stimulating hormone (alpha MSH) are important modulators of the immunologic response to tissue injury and antigenic challenge. Serial changes in the plasma concentrations of these two peptides were measured in 12 patients undergoing heart transplantation. Tissue concentrations of IL-6 in atrial samples from both donor and recipient hearts were also compared. Plasma IL-6 concentration remained stable prior to cardiopulmonary bypass (CPB), initially decreased with the onset of CPB, and then increased significantly over control values at the end of CPB (180 +/- 40 v 53 +/- 60 pg/mL). Plasma IL-6 remained elevated for at least 60 minutes after CPB, and then it returned to control values by 24 hours postoperatively (67 +/- 9 pg/mL). Examination of IL-6 changes after CPB in 10 additional patients undergoing nontransplant cardiac surgery with CPB revealed a similar elevation in IL-6 at 60 minutes after CPB (290 +/- 76 pg/mL). However, IL-6 in the nontransplant group remained significantly elevated at 24 hours (138 +/- 42 pg/mL). These combined results suggest that CPB causes a marked increase in IL-6, and that implantation of a new heart in transplant patients does not augment this increase. The return of IL-6 to control values by 24 hours in the patients who have had transplants suggests that immunosuppression has an appreciable effect on IL-6 at this time. In contrast to IL-6, plasma alpha MSH never increased above control values.(ABSTRACT TRUNCATED AT 250 WORDS)