Results from a number of studies suggest that beta-carotene-containing foods prevent the initiation or progression of various cancers. One possible mechanism for this effect could be enhancement of the immune response. The aim of this study was to determine whether beta-carotene modulates T lymphocyte subsets in patients affected with colonic polyps or cancerous lesions. Patients with previous adenomatous colonic polyps (n = 18) or colon cancers (n = 19) were randomized to receive placebo or beta-carotene (30 mg/day) for three months. Percentages of T lymphocyte subsets were determined using flow cytometry in blood samples collected before randomization and at three months. T lymphocyte subsets of 14 normal control subjects were also determined for comparison. Initially, there was no difference in total leukocyte counts, percentage of lymphocytes, and various subsets of lymphocytes among the three groups, although in cancer patients there was a lower percentage of CD4 and interleukin-2 (IL-2) receptor-positive (IL-2R+) cells than in patients with polyps and in controls. After supplementation with beta-carotene, a significant increase in IL-2R+ T lymphocytes (from 12.7 +/- 3.0% to 26.0 +/- 1.9%) and CD4+ lymphocytes (from 40.9 +/- 3.1% to 45.6 +/- 3.2%) was seen only in the cancer patients. These percentages remained unchanged in patients with adenomatous polyps receiving placebo or beta-carotene. We concluded that beta-carotene increased the number of IL-2R+ T lymphocytes and CD4+ lymphocytes, which in turn may produce IL-2 only in patients with cancer who may already have some deficiency in their immune system. This increase in activated T lymphocytes may mediate cytotoxic reactions to cancer cells via cytokine production.