AbstractInduction of mesoderm in ectodermal explants of Xenopus laevis blastula embryos had previously been shown to respond selectively to TGF-β2, with TGF-βs 1 and 5 having no activity in this assay. As TGF-βs 1, 2, and 3 are frequently coexpressed in tissues, we wished to examine the activity of TGF-β3 relative to that of TGF-βs 1 and 2 in this assay as well as in other in vitro assays. We report here that when the activity of recombinant TGF-β3 is normalized to that of TGF-β1 in the assay for growth inhibition in CCL-64 cells, it is also equal to that of TGF-β1 in assays for stimulation of both anchorage-independent growth of rat NRK cells and chemotaxis of human monocytes. In contrast, in the assay for mesoderm induction, recombinant TGF-β3 is 10-fold more active than TGF-β2, inducing expression of muscle specificα-actin at concentrations as low as 1 ng/ml. These results suggest that more complex systems, in contrast to individual cell types, may respond selectively to the various TGF-βisoforms and that there might be biological consequences of TGF-βisoform switching in vivo.