Although recent reports have described arachidonic acid metabolism of individual types of lung cells, the actual profile of eicosanoids that are produced in the lung may reflect interactions between different cell types. Because macrophages and epithelial cells are in close physical contact within the alveolus, we measured the eicosanoids produced by combined cultures of these cells. We found that the [14C]arachidonic acid that was released from previously labeled epithelial cells following A23187 stimulation was metabolized by alveolar macrophages to leukotriene B4 and 12-hydroxyeicosatetraenoic acid, which are products not normally produced by these epithelial cells. Simultaneously, there was a decrease in 6-keto-prostaglandin F1 alpha, the end product of prostacyclin metabolism and a major product of epithelial cell arachidonate metabolism but not macrophage arachidonate metabolism. A net increase in leukotriene B4 and a net decrease in 6-keto-prostaglandin F1 alpha were demonstrated by radioimmunoassay. Thus, the interaction of stimulated alveolar macrophages and epithelial cells alters the eicosanoid profile produced by each cell type alone in a manner that would tend to accentuate inflammatory processes within the alveolus.