We evaluated the effects of isoproterenol in right ventricular papillary muscles derived from normal and failing isolated human hearts. Basal values for the peak force developed, rate of force development (dF/dt), and time to peak tension (TPT) were similar in both groups. Isoproterenol produced a significantly smaller (p less than 0.05) increase in peak force developed and dF/dt in failing papillary muscles. The half equivalent dose (ED50) of isoproterenol was fivefold higher in failing muscle as compared to normal muscle. We conclude that failing cardiac muscle demonstrates decreased responsiveness to beta-receptor mediated stimulation.