There have been several case reports that erythromycin can prolong the QT interval, resulting in torsades de pointes. As magnesium is well established in the treatment of torsades de pointes, we aimed to investigate how this trace element influences the electrophysiological effects of erythromycin. The effects of erythromycin and magnesium on cardiac conduction and refractoriness were evaluated in isolated guinea pig hearts perfused by the method of Langendorff. Erythromycin was given in concentrations of 10, 30 and 100 microM. In the magnesium group MgSO4 was elevated to 3.4 mM. Magnesium at a concentration of 3.4 mM did not affect cardiac conduction and refractoriness. Erythromycin prolongs the QT interval in a dose-dependent manner. The prolongation of the QT interval by erythromycin was diminished by the elevated magnesium concentration (3.4 mM) at high rates (pacing cycle length 180 vs. 220 ms). The most pronounced effect of erythromycin (100 microM) was the prolongation of the atrial effective refractory period. This effect was nearly abolished by the elevated magnesium concentration (129.0 +/- 8.3% vs. 41.9 +/- 10.6%, P < 0.01, n = 6, x +/- SEM). In summary, magnesium minimizes the effects of erythromycin on the repolarization period in the ventricle and on the effective refractory period of the atrium.