Alveolar macrophages (AMs) play an important role in the regulation of the local immune reactivity in the lung. It was previously shown that exposure of rats to mild inescapable electrical footshock stress (20 min, 4 shocks/min, 5 s/shock, 0.8 mAmp) leads to apparent changes in the activity of AMs upon stimulation, reflected by an enhanced interleukin-1β and tumor necrosis factor-α secretion and decreased nitric oxide secretion compared with the secretion by AMs isolated from nonstressed rats. Here we show that in vivo blockade of the autonomic nervous system by intraperitoneal injection of the nicotinic receptor antagonist chlorisondamine leads to complete abrogation of these stress-induced alterations in AM activity. This role for the autonomic nervous system could further be attributed to sympathetic stimulation of β-adrenergic receptors as shown by blockade of β-adrenoceptors. Blockade of either α-adrenoceptors or parasympathetic output did not result in abrogation of the stress-induced changes in AM activity. The β-adrenergic modulation of AM activity most likely is not due to a direct effect of catecholamines on AMs because mimicking the in vivo stress effects by in vitro preincubation of AMs with various doses of catecholamines followed by lipopolysaccharide stimulation did not result in an altered cytokine secretion by AMs.