Patients (n='22) with metastatic or unresectable colorectal carcinoma were treated with interleukin (IL)-2 and lymphokine-activated killer (LAK) cells in a phase II study conducted by the IL-2/LAK Working Group (ILWG). Eligibility criteria for the study included bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. The median age of patients was 49 (range, 28-61) years. Eight (36%) patients had never received prior treatment other than their initial surgery; eight (36%) had received prior radiotherapy, and 12 (55%) chemotherapy. No patients had received prior immunotherapy. Treatment consisted of IL-2, 600,000 IU/kg administered by 15-min intravenous infusion every 8 h on days 1-5 and 12-16. Patients underwent 4-h leukapheresis on days 8—12, and cells were placed in in vitro culture with IL-2 for 3-4 days and the activated LAK cells were infused over 1 h on days 12, 13, and 15. AH doses of IL-2 and LAK cells were administered to patients in intensive care unit (ICU) settings. The mean ± SD number of IL-2 doses administered during days 1-5 was 13.4 ± 1.2, the mean number of LAK cells reinfused was 6.8 ± 2.2 x 10'°, and the mean number of IL-2 doses administered during the last phase was 9.8 ± 2.5. Nineteen patients completed the IL-2 priming phase and received at least one LAK cell infusion. One patient achieved a complete response and was progression free for 8 months from the beginning of treatment, for an overall objective response rate of 5% (95% confidence interval: 0-13%). Hypotension, weight gain, anemia, and elevations of serum creatinine and liver enzymes were common, but there were no treatment-related deaths. Treatment delivered and toxicity were comparable to those reported in studies conducted concurrently for other malignancies. We conclude that high-dose IL-2 has minimal activity in metastatic colorectal cancer; however, the low level of activity should not preclude future studies combining IL-2 with other immunotherapeutic approaches.