Major surgery impairs the cellular immune response. We have therefore studied the immunological effects of low-dose recombinant interleukin 2 given to patients undergoing surgery for colorectal cancer to determine whether this agent has potential in perioperative adjuvant immunotherapy. Patients were randomly allocated to control (n = 13) or treatment groups (n = 12). Immunological studies of both lymphocyte function and subset number were performed preoperatively and on Days 1, 4, 7, and 10. Treatment with recombinant interleukin 2 prevented the postoperative fall in both natural killer and lymphokine-activated killer cell cytotoxicity, clearly demonstrated in the control group. The treatment group also showed in vivo T-cell activation with an initial lymphopenia followed by a rebound lymphocytosis and upregulation of the subset markers CD25 (interleukin 2 receptor) and CD45RO (T-memory cells). These combined effects may have important consequences in controlling metastatic dissemination of tumor during the vulnerable perioperative period.