The effect of 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25(OH)2D3) on the expression of interleukin-2 (IL-2) receptor in activated T lymphocytes was examined. 1 alpha, 25(OH)2D3 enhanced the expression of IL-2 receptor (p55, Tac peptide) in phytohemagglutinin (PHA)-stimulated (3 days) human peripheral blood mononuclear cells (PBM) only in the presence of IL-2 without affecting the proliferation of the cells. This enhancement was dependent on the concentration of both IL-2 (0-1 U/ml) and 1 alpha, 25(OH)2D3(0-10(-7)M). The addition of interleukin-1 (IL-1, 0-100 U/ml), did not enhance the expression of IL-2 receptor in these cells in the presence of IL-2. Moreover, 1 alpha, 25(OH)2D3 had the same effect on two cell lines, Kit225 (an IL-2 dependent cell line established from a patient with T cell chronic lymphocytic leukemia) and YT (an IL-2 independent natural killer (NK)-like cell line from a patient with acute lymphocytic leukemia). Thus, 1 alpha, 25(OH)2D3 enhances the up-regulation of IL-2 receptor (p55) by IL-2 not only in activated T cells but also in the NK-like cell line.