This study examined the influence of BAY K-8644, a dihydropyridine Ca2+ agonist, on the positive inotropic effects of strophanthidin, isoproterenol, methoxamine and extracellular Ca2+ (Ca2+0) in atrial muscle isolated from guinea pig heart. BAY K-8644 enhanced both the maximum developed tension observed in the presence of strophanthidin and the sensitivity to its toxic effects. The maximum contractile force observed in the presence of methoxamine was also elevated by BAY K-8644 pretreatment; however, the ED50 value for methoxamine was not affected. The maximum contractile force elicited by BAY K-8644 alone or by strophanthidin or methoxamine in combination with BAY K-8644 was approximately the same as that produced by isoproterenol alone. The Ca2+ agonist did not alter the maximum developed tension elicited by increasing concentrations of isoproterenol or Ca2+0; however, it reduce both the ED50 for Ca2+0 and the concentration of isoproterenol necessary to produce maximum contractility. These results suggest that combinations of BAY K-8644 and cardiac glycosides can elevate contractile force to a level greater than that produced by cardiac glycosides alone.