Interleukin-2 (IL2) is essential for the expansion of antigen-triggered lymphocytes and cytotoxic T-cells, processes necessary for tumor control that are frequently depressed in malignancy. The authors measured certain aspects of IL2 function in cancer patients and controls and correlated the findings with the general immune response as indicated by the proliferative response to phytohemagglutinin (PHA) in peripheral blood lymphocytes (PBL). The major questions focused on the capacity of PBL to produce IL2, the correlation of this with the proliferative response to PHA, and whether exogenous IL2 could restore T-cell responses and natural killer cell activity in immunodepressed cancer patients. IL2 production was measured by the 3H-thymidine-labeled CT6 assay on the supernatants of the PBL of cancer patients and normal controls after 24 hours of stimulation with PHA. There were 115 cancer patients (70 head and neck, 13 melanoma, 12 breast, 10 colorectal, and 6 other) and 52 controls. IL2 production was essentially normal in the head and neck cancer patients as a group, although their PHA response was depressed. The mean IL2 generated per 3 X 10(6) PBL over 24 hours were 129 mu/ml in the head and neck patients and 132 mu/ml in the breast patients, similar to the 129 mu/ml generated in the controls. There was modest but not significant depression in the melanoma (78 mu/ml) and colorectal cancer patients (81 mu/ml). Although subsets of patients showed depressed IL2 production, there was no significant correlation of IL2 production with the PHA response. Depressed IL2 production showed only limited correlation with depressed lymphocyte responses (r = -0.25), which suggested a dissociation of these functions. Of interest was the finding that indomethacin did augment IL2 production in both cancer patients and controls, suggesting that prostaglandin-mediated regulation is involved. Addition of exogenous IL2 of recombinant origin (Biogen) produced significant augmentation in more than three fourths of the cancer patients and controls. Adding indomethacin further increased this response. Addition of IL2 also significantly increased natural killer activity in both groups. It was concluded that PBL in cancer patients generally have a normal capacity to generate IL2, and this capacity is not related to the proliferative response, which is frequently depressed in these patients. Exogenous IL2 can significantly augment lymphoproliferative and natural killer responses in cancer patients, suggesting that there is merit in exploring the potential therapeutic role of IL2 in these patients.