The lung macrophage is proposed to be involved in the development of asbestos-induced pulmonary fibrosis. Knowledge of the effects of long-term asbestos exposure on lung macrophage cytokine release should better define the role of the macrophage in fibrogenesis. This study examines the effects of acute in vitro asbestos exposure and chronic in vivo asbestos exposure on human alveolar macrophage cytokine release. As indicators of asbestos-induced macrophage activation, the cellular release of IL-1β TNF-α IL-6, GM-CSF, and PGE2 was mesaured during a 24-h in vitro culture. Alveolar macrophages from normal volunteers were cultured in vitro with chrysotile asbestos. Of the factors measured, only TNF-α was elevated in response to asbestos exposure. Alveolar macrophages from asbestos-exposed individuals were placed into one of two groups based on their exposure history. These two groups were matched for age, smoking history, and diagnosis; none met the criteria for asbestosis. Cells isolated from subjects that had been exposed to asbestos for more than 10 years secreted enhanced basal amounts of IL-10, TNF-α IL-6, and PGE2, while those who had been exposed for less than 10 years did not. The results indicate that while asbestos had minimal acute effects on cytokine production by the human alveolar macrophage, intense, chronic exposure to asbestos leads to the enhanced basal release of significant amounts of several cytokines that have activity for the fibroblast, even in the absence of overt fibrosis.