Serial changes in cardiac norepinephrine content and the β-adrenergic system were investigated during the development of cardiomyopathy in spontaneously diabetic Chinese hamsters (CHAD strain), in comparison to age-matched control Chinese hamsters (CHA) or non-diabetic CHAD hamster littermates. Cardiac norepinephrine content and 1-adrenergic receptor density significantly increased in short-term diabetics. These changes preceded both the development of cardiac hypertrophy and the enhanced response of adenylyl cyclase to isoproterenol plus 5'-guanylylimidodiphosphate [Gpp (NH)p], sodium fluoride, or forskolin stimulation. However, as the diabetic state developed cardiac norepinephrine content, 1-adrenergic receptor density, and adenylyl cyclase activity returned to control levels. The amount of stimulatory or inhibitory guanine nucleo-tide binding proteins in the diabetic group was similar to those in the control groups. These data suggest that the cardiac 1-adrenergic system is enhanced by the alterations in cardiac sympathetic activity during early diabetes, which are associated with the duration of diabetes rather than with the degree of hypertrophy or strain differences. (Jpn Circ J 1997; 61: 64 - 73)