We studied 104 patients after cardiac operations to search for changes in peripheral blood lymphocyte subsets, mitogen responsiveness, and interleukin-2 production. Mononuclear cells obtained from 10 patients with cholecystectomy were examined as control samples. Cultures for phytohemagglutinin and interleukin-2 production were incubated in microtiter plates for 24 hours with cells labeled with tritium thymidine used as target cells. Lymphocyte subsets were measured by using monoclonal antibodies. The results obtained with preoperative blood samples were compared with those from the first, third, and seventh days after operation. In patients having cardiac operations, mitogen responsiveness was low on both the first and the seventh days after operation and interleukin-2 production was markedly depressed (greater than 90% depressed) on the first postoperative day. However, in control samples from patients having cholecystectomy, lymphocyte subsets, mitogen responsiveness, and interleukin-2 production showed no significant changes. Improvement in interleukin-2 production occurred immediately in patients without blood transfusion from random donors and reached normal levels by postoperative day 3. However, interleukin-2 production remained depressed on day 3 in all patients with transfusion from random donors and remained significantly diminished even on day 7 in such patients in New York Heart Association classes III and IV. We conclude that heart operations for which cardiopulmonary bypass is used are associated with depression of cellular immunity, including interleukin-2 production. Furthermore, it appears that both blood transfusion from random donors and the general preoperative condition of the patients contribute to suppression of measures of cell-mediated immunity.