Using cultured normal human keratinocytes, we compared the activities of 1 alpha,24-dihydroxyvitamin D3 (1,25(OH)2D3), a biologically active form, in inducing cell differentiation. Treatment with 10(-6) M of 1,24R(OH)2D3 and 1,25(OH)2D3 increased the number of involucrin positive cells (differentiated from 6.4% to 24.1% and 25.1%, respectively. These results indicate that 1,24R(OH)2D3 has an ability comparable to that of 1,25(OH)2D3 to induce cell differentiation in human keratinocytes. The clinical effectiveness of 1,24R(OH)2D3 for the treatment of psoriasis may be, in part, related to its direct effect on hyperproliferative keratinocytes.