This study investigated the influence of the prototype beta(1) beta(2)-adrenoceptor antagonist propranolol and the novel carvedilol (beta(1) beta(2)- and alpha(1)-antagonist) on the thermogenesis of skeletal muscle ex vivo., During 1 week propranolol was given orally to 14 rats, 5 mg kg(-1) once daily, and carvedilol was given to 23 rats, 3 mg kg(-1) once daily; 19 rats received saline. Gastrocnemius muscle was obtained after decapitation. Carbogen-saturated Krebs-Ringer bicarbonate buffer containing glucose-insulin was pumped via heat exchangers through the microcalorimetric ampoule during the measurement, procedure, starting within 50 min after the biopsies, The results showed that the mean resting heat production at 37 degrees C was lower (p < 0.02, ANOVA) after propranolol, 0.45 mW g(-1) wet muscle, than after carvedilol, 0.63 mW g(-1), and also lower than in the control group (p < 0.05), 0.62 mW g(-1). Muscle ATP content was not changed and showed no relationship to the heat production. The muscle utilized approximate to 10% of its total energy for the Na-K pump as assessed by ouabain inhibition. In conclusion, the lower heat production from muscle in the free-fed rat after propranolol agrees with some human studies using whole-body oxygen consumption measurements. Carvedilol had no influence, probably because of its combined beta- and alpha(1)-blocking activity. The results indicate that the sympathetic nervous system is implicated in the regulation of resting skeletal muscle thermogenesis. Microcalorimetry of isolated muscle may help to understand the metabolic action of different adrenoceptor antagonists.