Diabetes can produce a state of hypothyroidism which is known to alter adrenoceptor activity in rat hearts. We studied the effect of six-week STZ-induced diabetes on responsiveness to adrenergic agonists and also determined if tri-iodothyronine (T3) treatment for 6 weeks could modify these responses. T3 treatment produced a marked tachycardia and a slight but significant decrease in serum glucose and serum lipids in diabetic rat. Methoxamine produced positive inotropic and positive chronotropic effects in untreated control left and right atria, respectively. These effects were significantly increased in untreated diabetic preparations. T3 treatment for 6 weeks in diabetic rats prevented this effect. Isoproterenol also produced a dose-dependent positive inotropic and positive chronotropic effect in untreated control left and right atria, respectively. These responses were attenuated in untreated diabetic preparations. T3 treatment by itself decreased the responsiveness to isoproterenol in control left atria and further decreased the responses to isoproterenol in diabetic left atria. Similarly, in diabetic right atria T3 treatment did not produce any alteration in the responses to isoproterenol. The results indicate that only some of the diabetes-induced alterations in adrenoceptor activity can be associated with hypothyroidism.