Intratracheal bleomycin induces pulmonary fibrosis in experimental animals, but the mechanisms involved are poorly understood. Since altered levels of fatty acid metabolites are associated with bleomycin-induced lung injury, we examined the effects of a change in dietary fat on bleomycin-induced fibrosis. Previously we have shown that an essential fatty acid-deficient diet can reduce the severity of bleomycin-induced pulmonary fibrosis. The present study examined the effect of replacement of usual dietary fat with menhaden oil, rich in eicosapentaenoic acid, on the development of pulmonary fibrosis. Weanling rats were raised on a standard laboratory diet or a diet consisting of a fat-free powder to which was added 25% (w/w) of menhaden oil. After 8 weeks of feeding, the animals received either 1.5 units of bleomycin or an equivalent volume of saline intratracheally. In animals receiving the laboratory diet, bleomycin treatment produced a 44% increase in total lung protein content when compared to saline-treated controls (p less than 0.001) and a 77% increase in total lung hydroxyproline content (p less than 0.01). In contrast, bleomycin-treated animals receiving the menhaden oil diet had only small increases, which did not reach statistical significance, in protein and hydroxyproline content in the lung. Bronchoalveolar lavage cellularity did not differ among the treatment groups, but the percentage of lavage macrophages was slightly diminished in bleomycin-treated animals receiving the laboratory diet. Cellular differentials of lavage fluid did not differ significantly between bleomycin- and saline-treated animals receiving the menhaden oil diet. Bleomycin-induced histologic changes, quantitated by morphometric analysis, were significantly reduced with the menhaden oil diet. We conclude that a diet rich in eicosapentaenoic acid can significantly ameliorate bleomycin-induced pulmonary fibrosis, possibly via alterations in eicosanoid metabolism.