Thymic hormones have been shown to exhibit immunorestorative effects in vivo and in vitro, and to enhance the expression of high affinity interleukin-2 (IL-2) receptors on normal human lymphocytes stimulated with phytohemagglutinin. Based on these data, a clinical trial was initiated to determine the effects of the combination of 5-fluorouracil (5-FU) and folinic acid (FA) with thymopentin (TP-5) and interleukin-2 (IL-2) in patients with advanced colorectal carcinoma. Fifteen patients were treated with FA, 200 mg/m2/day by IV bolus, and 5-FU, 400 mg/m2/day as a 30-minute infusion, both given for 5 consecutive days every 28 days. TP-5, 50 mg/day, was administered subcutaneously on days 8-11, and IL-2, 9 million IU/m2 twice daily, was given subcutaneously on days 12-16. Of 8 patients evaluable for response, 4 achieved a response. Two patients had stable disease, and two progressed during treatment. There were no instances of life-threatening toxicity. Two patients developed grade III stomatitis and diarrhea followed by leukopenia and fever, requiring hospitalization. Other toxicities were moderate. These results are only preliminary, and a larger number of patients and longer follow-up are needed to draw meaningful conclusions about the merits of this new approach in cancer treatment.