In the present work, we demonstrate that treatment with 1,25-dihydroxyvitamin D3 for 24 hours increased in a dose-dependent manner the levels of the two major insulin receptor (IR) mRNAs (11 and 8.5 Kb) present in U-937 human promonocytic cells. These levels reached maximum values (1.8-fold 11 Kb; 1.4-fold 8.5 Kb) with the addition of 10(-8) M 1,25-dihydroxyvitamin D3. In these optimal conditions the stimulatory effect of 1,25-dihydroxyvitamin D3 was accompanied by increases in both IR capacity, and insulin responsiveness for glucose transport in these cells. Moreover, such increases appear to be mediated by an enhanced expression of the receptor for 1,25-dihydroxyvitamin D3, measured at the level of both RNA and protein. These results provide evidence of 1,25-dihydroxyvitamin D3 acting as genomic stimulator of the insulin response in the control of glucose transport.