In order to investigate the possible modulation of macrophage function by the autonomic nervous system, the effect of adrenergic agonists and antagonists on interferon (IFN)--induced increases in cathepsin B (CB) in a macrophage-like cell line was studied. It has been shown previously that IFN-induces increased CB activity in phorbol myristate acetate (PMA)-primed THP-1 cells. Isoproterenol (ISO) (10 ), a mixed -receptor agonist, increased the induction of CB activity in the cells but norepinephrine (10 ) and epinephrine (10 ), the and receptor agonists, had little effect. The addition of the mixed -receptor antagonist phentolamine (10 ) had no effect on ISO induced increases but the mixed -receptor antagonist propranolol (10 ) and the selective 1 -receptor antagonist atenolol produced significant inhibition. These results suggest that the activation of -receptors could be involved in the induction of CB activity in macrophages and provide a possible mechanism for the regulation of macrophage effector function by the autonomic nervous system. Dibutyryl cAMP (1 m) alone also induced increases in CB in THP-1 cells, and H-89 or HA1004 abrogated the effect of dibutyryl cAMP, suggesting that the effect of ISO on CB could be through the elevation of cAMP and the activation of cAMP-dependent protein kinases.