Four rat strains and hamsters were exposed to 0.7 mg crocidolite asbestos/g lung once/week for 3 weeks by intratracheal instillation (IT). Pulmonary function, biochemistry, and morphometry were evaluated at 3 and 6 months after IT. Each rat strain, but not the hamster, exhibited elevated lung volumes. Quasistatic compliance in rats and hamsters was reduced 15%-40% and 25%-50%, respectively. Diffusing capacity for carbon monoxide was elevated in the rats, but in hamsters, it was reduced at both time points. Hydroxyproline was increased in the rat strains but not in hamsters. Lung protein/dry weight was not altered in most of the rat strains and in hamsters at both time points. The linear mean intercept value was increased in Fischer 344 (F344) rats (3 and 6 months) and Long Evans rats (6 months), whereas in hamsters only at 6 months. Surface area was unchanged in both species. Specific density for parenchymal tissue was reduced for F344 rats at both time points, but alveolar density values did not change overall relative to species and time. The correlated functional and morphological changes in the hamster appeared more consistent with human asbestosis. Divergent lung responses in different species and strains should be considered when selecting laboratory animal models for studies related to asbestos exposure.