Postnatal changes in sensitivity to norepinephrine (NE) were studied in normal and sympathectomized rat hearts. The sensitivity of left atria to NE was highest at birth, after which it declined, reaching the adult level by 2 weeks of age. Developmental changes in NE sensitivity of the left atria seemed to be related to the density of sympathetic innervation, and the high sensitivity at birth was most likely due to the lack or immaturity of the uptake function of the nerve endings. In contrast to the atria, right ventricular papillary muscle did not change in NE sensitivity with age. Immunological and chemical sympathectomy was performed by repetitive administration of antiserum to nerve growth factor and 6-hydroxydopamine, respectively. Both atria and papillary muscles from immunologically and chemically sympathectomized rats were supersensitive to NE at all ages tested. Inasmuch as the supersensitivity to NE was most marked at the 4th week of age, atria of this age were used for the study on the mechanisms of supersensitivity. Left atria from sympathectomized 4-week-old animals were also supersensitive to isoproterenol and phenylephrine. Because isoproterenol and phenylephrine are not taken up into sympathetic nerve endings, it was concluded that the postjunctional mechanisms were involved in the genesis of the denervation supersensitivity of left atria.