The effects of adrenergic stimulation of the anti-mycobacterial activity of peritoneal macrophages was investigated. We found that epinephrine and norepinephrine stimulated macrophages to suppress the growth of Mycobacterium avium. Stimulation was mediated by binding to the alpha 2 adrenergic receptor. The addition of the alpha 2 agonist clonidine to cultures resulted in an inhibition of mycobacterial growth and the effect of epinephrine was blocked by the alpha-antagonist phentolamine. Treatment of the macrophages with propranolol, a beta-antagonist, potentiated the effect of epinephrine. Epinephrine mediates its effect by stimulating the expression of macrophage activation genes.