The pathological lesions of bagassosis have been reproduced in guinea pigs given bagasse fibers along with low doses of actinomycete spores. In the early stages, interstitial infiltration with lymphocytes and macrophages as seen in humans was noted. Later, small interstitial bagasse granulomas composed of foreign body giant cells, fibroblasts, and lymphocytes developed, some of which had a laminated appearance. Lymph node changes consistent with an immunological reaction were observed. Actinomycetes alone showed occasional areas of pneumonitis and bagasse alone small granulomas consisting of foreign body giant cells and bagasse fibers. Finally, the combined effect of dust and actinomycetes produced interstitial fibrosis composed of thick reticulin fibers and occasional collagen fibers, which persisted to the end of the experiment. Bagasse alone and actinomycetes alone produced only thin reticulin fibers. It has been suggested that bagassosis is due to the synergistic action of bagasse fibers and Micropolyspora faeni and that in the pathogenesis of the syndrome an immunological component may be involved.