To study the effect of blood transfusion (BT) on cell-mediated immunity, we examined the antigen presentation function of peritoneal macrophages and interleukin 2 (IL-2) generation by splenocytes. C3H/HEJ mice were transfused with 0.2 mL of fresh allogeneic blood obtained from C57BL/6 mice; they were killed on days 1, 3, and 7 after BT. A second group of C3H/HEJ mice was transfused with 0.2 mL/d of the same allogeneic blood on three successive days; they were killed on day 7 following the last BT. The antigen presentation function of peritoneal macrophages was measured by utilizing a D10.G4.1 T-helper cell clone; IL-2 activity in supernatants of concanavalin A—stimulated splenocytes was tested by utilizing an IL-2-dependent HT-2 cell line. The results indicate that although antigen presentation function remains unaffected after single and multiple BTs, the ability of splenocytes to generate IL-2 decreases significantly even after a single BT. Thus, the increased susceptibility to infection and the additional immune perturbations in malignant neoplasms following BT may be due in part to decreased IL-2 generation. © 1988, American Medical Association. All rights reserved.