Transforming growth factor beta 1 (TGF beta 1) is a regulator of cell proliferation and differentiation. Using a mouse peritoneal cell-derived mast cell culture system, we investigated the effects of TGF beta 1 on mast cell proliferation. TGF beta 1 inhibited IL-3- and IL-4-dependent connective tissue-type mast cell proliferation. The effect was concentration dependent: 50% inhibition was observed with 1.0 ng/ml TGF beta 1 and the maximal inhibitory effect (no proliferation), was observed with 10 ng/ml. Flow cytometric analysis suggested that the inhibitory effect of TGF beta 1 was due to blocking of both G1 and G2 phases. Both control and TGF beta 1-treated mast cells showed similar histamine release induced by the calcium ionophore, A23187. TGF beta 1 seems to be an important negative regulator of connective tissue-type mast cell proliferation with apparently no appreciable effect on mast cell function.