The effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on proliferation and collagen type I and type III production in cultured human fibroblasts was examined. Previous studies have identified receptors for the vitamin in human dermal fibroblasts, and have suggested the skin to be a target tissue. While many studies examining keratinocyte modulation by 1,25-(OH)2D3 have been undertaken, very few have been performed on dermal fibroblasts. Neonatal foreskin fibroblast cultures were examined for cell number, extracellular collagen accumulation, and collagen mRNA levels, after 5 days exposure to 1,25-(OH)2D3 at a concentration of 10(-7) M. The vitamin significantly suppressed (P < 0.01) the proliferation of fibroblasts cultured in the presence of serum. Day 5 cell culture supernatants showed a significant per cell increase in collagen type I (P < 0.05) and type III (P < 0.01) as measured by ELISA. Type I collagen production in exposed cells was 11.64 + 0.531 microgram/10(6) cell vs. 9.53 + 0.500 microgram/10(6) cells in unexposed cells. Type III collagen production was 0.601 + 0.012 microgram/10(6) cell in exposed cells and 0.247 + 0.008 microgram/10(6) cells in unexposed cells. mRNA levels were increased after a 4-day exposure to 10(-7) M 1,25-(OH)2D3 for both type I (2.5-5-fold) and type III (5.5-7.76-fold) collagen. These results suggest a novel effect of increased collagen production by dermal fibroblasts upon exposure to 1,25-(OH)2D3 that is independent of proliferation.