Treatment of rats with monocrotaline (MCT) or its reactive pyrrole metabolite, dehydromonocrotaline (MCTP), injures pulmonary capillary endothelium and other lung cell types. The mechanism by which pulmonary damage occurs is unknown. To investigate the possibility that the metabolites of MCT can injure lung cells directly, slices of lung from male Sprague-Dawley rats were incubated with chemically synthesized MCTP (0.1-1.0 mM). The ability of the slices to accumulate 5-hydroxytryptamine (5HT) was then examined. After 5 hours exposure to MCTP in vitro, there was no change in either 5HT or PQ uptake at any of the MCTP concentrations tested. Similar results were obtained when lung slices were incubated with liver slices and MCT to generate MCT metabolites in vitro. In contrast, treatment in vivo with MCTP resulted in a 35% decrease in the uptake of 5HT and a 15% decrease in the uptake of PQ by lung slices 14 days after treatment. These results suggest that damage does not occur by direct interaction of MCTP with the lung tissue or that functional injury is slow to develop. Alternatively, the damage in vivo may be mediated by factors not present in the sliced tissue.