Exercising men, compared with women, have a greater increase in leucine oxidation but not lysine rate of appearance. The cause for this sexual dimorphism is unknown; however, an inhibition of beta-adrenoreceptor activity has previously been shown to mediate amino acid metabolism (Lamont LS, McCullough AJ, and Kalhan SC. Am J Physiol Endocrinol Metab 268: E910 - E916, 1995; Lamont LS, Patel DG, and Kalhan SC. J Appl Physiol 67: 221 - 225, 1989). This study was a gender comparison of leucine and lysine kinetics during a beta-adrenoreceptor blockade (beta(1),beta(2)-blockade) and a placebo control by using a double-blind crossover protocol. Subjects exercised at 50% of their trial-specific maximal O-2 consumption ( 1 h) after 7 days of dietary control. During exercise with beta-blockade, men had an increased nonprotein respiratory exchange ratio ( P < 0.001), whereas women had an increased circulation of free fatty acids ( P < 0.001). The genders also displayed distinct differences in exercise amino acid kinetics. The men, but not the women, increased leucine oxidation ( P < 0.005) and lysine rate of appearance ( P < 0.009) when exercising during beta-adrenergic blockade. This study indicates that during beta-blockade, exercising men increase their need for amino acids ( and carbohydrate) to fuel energy needs, whereas women increase their mobilization of fat, thereby requiring less alternative fuels such as carbohydrate and amino acids. Gender-specific fuel preferences during exercise are regulated by beta-adrenergic-receptor activity. Substrate availability during exercise appears to modulate the amino acid oxidation differences between genders.