The effect of magnesium ion on the abnormal pacemaker activity of guinea pig ventricular muscle cells depolarized by 27 mM K+ was studied. Isoproterenol produced a small depolarization in the resting membrane and elicited automatic repetitive action potentials at higher concentrations in the presence of 0.2 mM Ba2+. This model was used to assess the antiarrhythmic effect of magnesium ion on cardiac muscle cells. Isoproterenol concentrations needed for depolarization alone or for depolarization plus automatic activity were taken as a basis for evaluation. The responsiveness of muscle cells to isoproterenol was suppressed significantly by increasing the magnesium concentration. It is concluded that magnesium ion may have an antiarrhythmic effect on partially depolarized cardiac muscle cells.