The use of isocyanates in industry has been increasing and, therefore, the potential for human exposure has also increased. Two such isocyanates are diphenylmethane-4,4'-diisocyanate (MDI) and dicyclohexylmethane-4,4'-diisocyanate (SMDI). Furthermore, there are only a few reports describing the toxicity of these diisocyanates. The pulmonary irritation of the aromatic isocyanate MDI and the sensory and pulmonary irritation of the cycloaliphatic isocyanate SMDI were studied in an animal bioassay. Groups of male, Swiss-Webster mice were exposed to aerosol concentrations of MDI varying from 17 to 67 mg/m3. The total exposure time for both isocyanates was 240 min, and the respiratory patterns and frequency of four mice were recorded during each exposure. Concentrations of MDI and SMDI in the exposure chamber were determined gravimetrically. The mass median aerodynamic diameter (MMAD) and geometric standard deviation for the MDI aerosol were 0.7 micron and 1.6 and for the SMDI aerosol were 0.9 micron and 1.5, respectively. The inhalation responses during the 4-hr exposures to aerosols of MDI and SMDI were investigated, and the animal model was used to determine time-response and concentration-response relationships for all exposures. From these results it was determined that the level of effect was dependent on both the duration of exposure and the exposure concentration. Unlike many other isocyanates tested with this animal model, MDI and SMDI acted primarily as pulmonary irritants, evoking little or no sensory irritation. The concentrations required to reduce the respiratory rate 50% (RD50) due to pulmonary irritation was 32 mg/m3 for MDI and 40 mg/m3 for SMDI. Increases in lung weight were found in groups of animals killed 24 hr following all exposures to MDI and SMDI. Using the animal model, which has been calibrated to human responses with nitrogen dioxide and other pulmonary irritants, the recommended TLV-TWAs for MDI and SMDI in industry should be no higher than 0.3 and 0.4 mg/m3, respectively.