1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(OH)2D3), alters the proliferation of keratinocytes in cell culture. To assess whether changes mediated by 1 alpha,25(OH)2D3 in keratinocyte growth are due to the release of transforming growth factors beta (TGFs beta), we measured TGF beta 1 and 2 in human keratinocytes treated with 1 alpha,25(OH)2D3. We showed that the inhibition of keratinocyte growth by 1 alpha,25(OH)2D3 was associated with a time- and dose-dependent increase in the concentrations of TGF beta 2 but not TGF beta 1. There was a strong correlation between the inhibition of cell growth and the increase in TGF beta 2 concentrations. Antibodies directed against TGF beta 1, 2 and 3 partially blocked the inhibition of cellular growth mediated by 1 alpha,25(OH)2D3. We conclude that 1 alpha,25(OH)2D3 inhibits human keratinocyte cell growth by a mechanism that involves, at least in part, an increase in the release of TGF beta 2.