Age-related changes in the response of rabbit papillary muscles to isoproterenol and calcium were studied. Newborn rabbit papillary muscles were not only less sensitive to the inotropic effect of isoproterenol and calcium, but also produced significantly less maximal inotropic tension to these agents in comparison to the adult. The decreased response of newborn papillary muscle to isoproterenol appears to be due to a combination of (a) decreased ability of papillary muscle to respond to calcium and (b) immaturity of isoproterenol-sensitive contractile mechanism. Differences in myocardial norepinephrine content do not appear to play an important role in the age-related difference in the response to isoproterenol and calcium.