Thyroid hormones and beta-blockers both affect energy balance and the heart. The interaction of 3,5,3'-triiodothyronine (T3) and the beta-blocker atenolol on some cardiac and energy balance parameters was therefore investigated. Stock-fed male Wistar rats (approximately 400 g) received 5 micrograms (expt 1) or 1.5 micrograms (expt 2) T3.100 g body wt-1.day-1 for 3 wk, with or without atenolol. In expt 3, rats were overfed with a "cafeteria" diet before and during the experiment and otherwise treated as in experiment 2. Compared with stock-fed (expt 1 and 2) or overfed (expt 3) controls, T3 caused an increase in food intake in experiments 1 and 2 but not in experiment 3. There was a large loss of body fat in all experiments, disproportionately greater than the body weight loss. Protein loss was significant only in experiment 1 and negligible in cafeteria rats. Heart rate and weight were increased, although heart composition remained unchanged. Atenolol, in a dose that abolished T3-induced tachycardia, did not modify any of the other T3 effects investigated, including the hypertrophy of the heart. These results indicate that T3-induced tachycardia can be abolished by concomitant treatment with a beta-blocker without altering parameters connected with energy balance, whereas protein loss caused by T3 can be attenuated by lowering the dose of T3 used and can be further blunted by dietary manipulation (cafeteria overfeeding).