The effect of beta 1- or beta 2-antagonism on the plasma levels of glucose, lactate, triglycerides, and free fatty acids was studied in seventeen normal male volunteers. All subjects performed three graded and uninterrupted exercise tests until exhaustion. Prior to each exercise test they received in a randomized order during three consecutive days either placebo or a predominant beta 1-blocker (atenolol, 50 mg once per day) or a predominant beta 2-blocker (ICI 118,551, 20 mg t.i.d.), according to a double-blind cross-over study design. Atenolol increased the plasma level of glucose at rest but did not influence the rise in plasma glucose during exercise. ICI 118,551 did not change the resting plasma glucose level, but it prevented the exercise-induced rise in plasma glucose, observed during placebo. During beta 1-antagonism the plasma lactate concentration at rest and during or after exercise was not different from placebo. During beta 2-blockade the exercise-induced rise in plasma lactate tended to be suppressed, and during recovery the plasma lactate levels were significantly lower than during placebo. The serum triglycerides concentration at rest and exercise was not altered, either by beta 1- or by beta 2-antagonism. Atenolol and ICI 118,551 did not affect the serum level of free fatty acids at rest, but at moderate exercise the serum free fatty acids concentration was lower during beta 1-blockade than during placebo. Our results provide further evidence that beta 2-adrenergic receptors are involved in the regulation of the plasma levels of glucose and lactate during exercise.