The production of cytokines by alveolar macrophages was studied after exposure of rats to an acute stress paradigm (mild inescapable footshocks). When alveolar macrophages from nonstressed animals were isolated and cultured, they readily produced interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) after stimulation with lipopolysaccharides (LPS). For these cytokines the dose response relationship for LPS was clearly biphasic. Nitric oxide (NO) production could only be detected upon LPS stimulation and seemed to be monophasic. However, when the animals were exposed to the acute stress paradigm, isolated alveolar macrophages (AM) showed a marked increase of IL-1 beta and TNF-alpha secretion upon LPS stimulation in vitro, but no changes in the production of IL-6 were detected. In contrast, exposure to the stress paradigm resulted in a strong decrease in NO production. The results indicate that emotional stress can rapidly induce altered behavior of AM, which is discussed in view of the important role these cells play in the regulation of the local immune responses in the lungs and the possible contribution to asthma.