alpha-Thrombin (TH) initiates a program of intracellular events that lead to DNA replication in quiescent CCL39 Chinese hamster lung fibroblasts via membrane receptors that have yet to be characterized at a molecular level. Functional TH receptors were expressed in Xenopus laevis oocytes following injection of poly(A)+ RNA from TH-responsive CCL39 cells; their presence was demonstrated by TH-stimulated 45Ca2+ efflux or Ca2(+)-dependent Cl- channel activation. In voltage clamp experiments on microinjected oocytes a Ca2(+)-activated Cl- current was detected in response to TH (0.2-10 U/ml). The TH response was blocked by a specific TH inhibitor, and potentiated by addition of FGF or intracellular injection of GTP-gamma-S.