Specific receptors for calcitriol (1,25-dihydroxyvitamin D) have been found in immune cells, such as monocytes and activated lymphocytes, suggesting that calcitriol may play an immunoregulatory role. In fact, a marked increase in lymphocyte proliferation has been reported after treating hemodialyzed patients with 1α-hydroxyvitamin D<sub>3</sub>, a precursor of calcitriol. We have studied in vitro the effect of calcitriol depletion and calcitriol addition on the phytohemagglutinin-induced mitogenesis of peripheral blood mononuclear cells from 14 healthy subjects and 8 hemodialyzed patients. The calcitriol depletion of culture medium did not modify cell proliferation. The addition of calcitriol in concentrations about the physiological range (10<sup>-11</sup> M) induced a small, marginally significant, 11% increase in the poliferation of lymphocytes from hemodialysis patients. Supraphysiological concentrations (10<sup>-9</sup>-10<sup>-7</sup> M) induced a marked inhibition (up to 60% of control values) of cell mitogenesis, both in patients and in healthy subjects. These results suggest that the increase in lymphocyte proliferation observed in vivo after treatment with calcitriol precursors is not mediated by a direct effect of calcitriol on circulating mononuclear cells.