Transforming growth factor‐β1 (TGF‐β1) is a potent growth inhibitor for many cell types. On fibroblasts, TGF‐β1 has been shown to inhibit human platelet‐derived growth factor (PDGF)‐induced mitogenicity. The mechanism implicated in this growth inhibition is unknown. In this work, we show on human bone marrow fibroblasts that TGF‐β1, which inhibited PDGF‐BB mitogenicity, was able to block PDGF‐BB‐induced early events such as polyphosphoinositide (Ptdlns 4,5‐P₂, Ptdlns 4‐P, and Ptdlns) breakdown and Ins 1,4,5‐P₃ formation. No significant modification by TGF‐β1 of PDGF‐BB binding (n₁ = 200,000 vs. n₂ = 195,000 sites per cell with TGF‐β1; Kd₁ = Kd₂ = 0.5 × 10⁻⁹M) and of internalization kinetics was observed. In addition, TGF‐β1 was shown to inhibit PDGF‐BB receptor autophosphorylation either in intact cells or in partially isolated membranes and to partially inhibit PDGF‐R tyrosine kinase activity. Since a dephosphorylation mechanism through protein phosphatases could be implicated, we used okadaic acid, a potent inhibitor of type 1 and 2A serine/threonine phosphatases and showed that okadaic acid restored PDGF‐receptor autophosphorylation on tyrosine residues. Based on these data, we suggest that an alternative regulatory mechanism of PDGF tyrosine phosphorylation seems to involve serine/threonine phosphatase activation. © 1992 Wiley‐Liss, Inc.