The interaction of fibroblasts, macrophages, and crocidolite asbestos fibers was studied in cell culture. We determined the effects of co-cultivation and asbestos fibers on collagen, total protein, and PG production. The co-cultivation of guinea pig alveolar macrophages and fetal lung fibroblasts resulted in a 155% increase in protein and a 31% increase in collagen production above fibroblast controls. The collagen was derived exclusively from the fibroblasts. Although total protein production was derived predominantly from the fibroblasts, the macrophages in co-culture also contributed to the protein levels. The addition of asbestos fibers to fibroblast cultures resulted in a decrease in collagen and total protein production. The addition of asbestos fibers to fibroblast and macrophage co-cultures prevented the enhancement of collagen production and limited the increase in protein production above fibroblast controls. PGE2, PGI2, and TXA2 were measured in macrophage and fibroblast cultures. Very low, almost undetectable PG production was observed under basal conditions by either cell type alone or in co-culture. Bradykinin induced release of these PGs in fibroblast but not macrophage cultures. This release was enhanced in co-cultures. Asbestos fibers, when added to the co-cultures caused a significant increase in the release of PGs, particularly PGE2. PGE2 is known to inhibit collagen and total protein production by fibroblasts. The increased release of PGs in asbestos-treated co-cultures may have contributed to the described asbestos suppression of collagen production