Surgery and blood transfusions have both been reported to cause decreases in various measures of cell-mediated immunity. A study of in vitro T helper lymphocyte type 2 (Th2) cytokine secretion after major joint replacement surgery was performed because these cytokines (IL4 and IL10) generally down-regulate cellular immune function. Th1 cytokines such as IL2 tend to up-regulate cellular immunity. Forty-three patients undergoing elective joint replacement surgery had pre- and multiple post-operative levels of IL2, IL4 and IL10 secretion measured and analysed with regard to demographic and clinical outcome data. Total joint replacement alone without allogeneic transfusions led to substantial increases in peak mean IL4 (2.1 times the pre-operative level) and IL10 secretion in vitro (4.3-fold) compared with much more modest increases in IL2 (1.36-fold) (P < 0.0001 for changes from baseline for each cytokine). In 14 patients who received allogeneic transfusions, these changes were greater than those in recipients of only autologous blood for IL4 (5.0-fold; P = 0.0036 vs. no allogeneic transfusion) and IL10 (15.7-fold; P = 0.079) but not for IL2 (1.38-fold; P = 0.38). The dramatic increase in Th2 cytokine secretion and minimal change in Th1 cytokine secretion after total joint replacement, with or without allogeneic transfusions, was seen regardless of type of anaesthetic, duration of surgery or whether knee or hip replacement occurred. These changes in cytokine patterns may contribute to the decreases in cellular immune function seen after surgery. Allogeneic transfusions but not autologous transfusions appear to exacerbate this immune deviation toward a T helper 2 (Th2) type response, and thus probably contribute to down-regulation of cellular immunity in the setting of joint replacement surgery.