1,3-Butadiene (BD) is oxidized by cytochrome P450 to reactive metabolites, including 1,2-epoxy-3-butene (BMO) and 1,2:3,4-diepoxybutane (BDE), which are thought to be responsible for BD genotoxicity and carcinogenicity. Alveolar-bronchiolar neoplasms were observed in mice but not rats following chronic exposure to BD. The site-specific carcinogenicity of BD in mice may result from metabolic activation in pulmonary tissue. We have incubated bronchioles isolated from both male B6C3F1 mice and male Sprague-Dawley rats with 34 microM BD (final concentration in the aqueous reaction medium) to assess species differences in pulmonary metabolism of BD and to enhance our understanding of species- and site-dependent BD carcinogenicity. Bronchioles from both mice and rats formed BMO, although mouse tissue produced 2-fold more than rat tissue. These preliminary results suggest that pulmonary activation of BD may play a role in the carcinogenicity of BD following inhalation exposure; however, other factors in addition to metabolic differences, probably contribute to the observed differences in susceptibility to BD toxicity.