The effect of TGF-beta 1 on the expression of alkaline phosphatase (ALPase) activity was examined during osteoblastic cell line (MG-63) differentiation induced by 1,25-dihydroxyvitamin D3 (1,25D3). TGF-beta 1 and 1,25D3 were found to enhance ALPase activity. However, preincubation of the cells with 1,25D3 transiently abolished the effects of TGF- beta 1. Kinetics of the complex responses to TGF- beta 1 and 1,25D3 were found to correlate well with that of the expression level of type II receptor for TGF- beta. These results suggest that 1,25D3 may regulate the cellular responses to TGF- beta 1 in part via regulation of functional receptor for TGF- beta.