OBJECTIVE: This study was undertaken to evaluate the effects of magnesium sulfate (MgSO4) on contractile force and increases in free intracellular calcium concentration ([Ca2+]i) in human myometrial strips from pregnant women. STUDY DESIGN: Simultaneous measurements of isometric tension and [Ca2+]i were measured in myometrial strips obtained at the time of cesarean delivery from pregnant nonlaboring women at term with the use of a fluorescence spectrometer equipped with a displacement force transducer. Changes in [Ca2+]i were measured with fura-2, a Ca(2+)-sensitive fluorescent probe. Myometrial strips were exposed to MgSO4 (5 or 10 mmol/L) for 5, 10, 20, and 30 minutes and observed for spontaneous contractions or stimulated with either oxytocin (OT; 0.1 micromol/L) or potassium chloride (KCl; 90 mmol/L). RESULTS: MgSO4 reduced spontaneous, OT, and KCl-evoked contractions and increases in [Ca2+]i in a time and concentration-dependent manner. After 20 minutes exposure to 5 mmol/L MgSO4, the OT-elicited changes in contractile response and [Ca2+]i were significantly decreased. MgSO4 did not change [Ca2+]i/force relationship of the responses to OT or KCl, or during spontaneous activity. CONCLUSION: At a pharmacologic concentration (5 mmol/L), MgSO4 inhibits contractile response and [Ca2+]i in pregnant human myometrial strips by a pattern that is consistent with both extra- and intracellular mechanisms. At a suprapharmacologic concentration (10 mmol/L), the more immediate effect of MgSO4 is consistent with an extracellular mechanism. MgSO4 does not appear to interfere at the level of the calcium-calmodulin interface, since the [Ca2+]i/force relationship was not changed.