Bleomycin treatment has been used for the experimental induction of pulmonary fibrosis, but the mechanisms involved are poorly understood. Since alterations in the levels of certain fatty acid metabolites have been associated with bleomycin-induced lung injury, we examined the effects of different dietary fats on the development of bleomycin-induced pulmonary fibrosis. Weanling rats were raised on standard laboratory feed or a diet consisting of a fat-free powder to which was added either coconut oil or beef tallow (25% w/w). After 8 weeks of feeding, animals received either 1.5 units bleomycin or an equivalent volume of saline intratracheally. Bleomycin treatment resulted in significant increases in total lung hydroxyproline content in the groups fed the standard lab diet (p less than 0.001) and beef tallow diet (p less than 0.001), but not in the group receiving the coconut oil diet. Furthermore, the lung hydroxyproline content in bleomycin-treated animals was less with the beef tallow diet compared with standard lab feed (p less than 0.05). Bleomycin treatment resulted in an increase in thiobarbituric acid-reactive products, an index of lipid peroxidation, in lungs from animals fed the standard lab diet, but not in the other diet groups. The percentage of diseased lung, as determined by morphometric analysis, was increased in bleomycin-treated animals from all diet groups (p less than 0.05). We conclude that alterations in dietary fats can reduce the severity of pulmonary fibrosis resulting from bleomycin treatment. Possible mechanisms for this effect include alterations in eicosanoid metabolism or changes in immune or effector cell function.