We studied the inotropic effect of the α-agonist phenylephrine on human and rat myocardium in relation to age. Strips of human atrial myocardium, discarded during cardiac surgery, were obtained from pediatric (2 to 18 months) and adult (40 to 60 yr) patients, and their electrically driven contractions were studied. The inotropic response of pediatric myocardium to phenylephrine was five times larger than that of the adult myocardium (p< .05). The β-agonist, isoproterenol, was also administered to the same myocardial specimens, and the average pediatric myocardial response was three times larger than that of the adult myocardium (p< .05). Strips of right ventricular myocardium were obtained from four age groups of rats: 14 days, 3 months, 6 months, and 18 months, and exposed to phenylephrine. We demonstrated two age-related phenomena: a) a biphasic response with an early short negative inotropic effect preceding a sustained positive inotropic effect was registered in most of the rats aged 3 months and older, but in none of the youngest age group, b) A high mean positive inotropic response (211% of basal response) was generated in the youngest age group, whereas the oldest age group of rats showed only a slight response (8% of basal response,p< .05). We conclude that loss of myocardial responsiveness to α and β-agonist with increasing age is a prominent feature. The pattern of the ventricular responsiveness to phenylephrine also changes during aging as it turns from monophasic to biphasic.