OBJECTIVE: The purpose of this study was to investigate changes in cell-to-cell coupling of human myometrium during pregnancy to assess the presence and permeability of gap junctions. STUDY DESIGN: To evaluate the coupling, input resistance was measured and intercellular spread of Lucifer yellow was observed with microelectrode techniques in intact myometrial preparations from four nonpregnant women, 13 women not in labor, and three women in labor. Octanol, isoproterenol, and dibutyryl adenosine 3',5'-cyclic monophosphate were applied to the preparations to assess their effects on cell-to-cell coupling. RESULTS: Input resistance of myometrial cells was decreased (p < 0.001) and intercellular spread of Lucifer yellow was increased during pregnancy. Octanol, isoproterenol, and dibutyryl adenosine 3',5'-cyclic, monophosphate rapidly and reversibly increased input resistance (p < 0.001 for all these agents) and blocked Lucifer yellow spread in tissues from pregnant patients. CONCLUSIONS: Cell-to-cell coupling between human myometrial cells is spontaneously improved during pregnancy because of the presence of gap junctions. The coupling is rapidly and reversibly decreased by octanol, isoproterenol, and dibutyryl adenosine 3',5'-cyclic monophosphate as a result of decreased permeability of gap junctions. These two methods of modulation of gap junctions are suggested to be major mechanisms for control of myometrial contractile activity in the human uterus during pregnancy.