The effects of prednisolone in the concentrations of 1, 10, 20, and 40 p,glml on the simultaneously recorded action potential and contractility of human atrial muscles obtained from patients undergoing corrective open heart surgery were studied for 20 to 45 minutes. 1n the concentration of 1 p,glml, prednisolone was ineffective in producing any changes in action potential and contraction in the muscles, but in higher concentrations (10,20, and 40p,glml) it produced concentration-dependent decreases in contractility and amplitude of action potential, and it lengthened duration of action potential. The effects appeared within 5 minutes. The per cent decreases in the contractility at the end of 20 minutes were approximately 7, 37, and 47 with 10, 20, and 40 p.glml of prednisolone, respectively. It depressed conduction in the atrium. The effects of prednisolone were reversible. Ouabain in similar preparation shortened the duration of action potential and increased contractility. Prednisolone, 40,p.glml, abolished the ouabain-induced positive inotropic effect. It appears that prednisolone affects contractility and action potential duration through stimulation of NaLK+-ATPase. Its probable involvement in the genesis of congestive heart failure and the poor response of digitalis in congestive heart failure in Cushing's syndrome are discussed.