An exposure system that allows large-scale exposure of animals to 1,6-hexamethylene diisocyanate (HDI)-based polyisocyanates at a stable concentration and aerosol size distribution was developed. The HDI polyisocyanate aerosol is generated by nebulizing a solution of a commercial polyisocyanate product dissolved in acetone. The aerosol is delivered with a constant airflow into a horizontal flow chamber. Complete mixing of aerosol in the chamber is ensured by a circulating fan. This method has been used to generate atmospheres containing HDI polyisocyanates at a concentration of 10.46+/-0.23 mg/m(3) over a 5-hour period. The overall mass median aerodynamic equivalent diameter was found to be 1.42 microm with a geometric standard deviation of 1.26. The HDI monomer concentration was 0.15+/-0.04 mg/m(3). The average chamber acetone concentration was determined to be 2481+/-222 ppm (mean+/-standard deviation). Different HDI polyisocyanate concentrations in the chamber can be achieved by altering the concentration of the commercial polyisocyanate product in acetone and the chamber flow rate. The described exposure system will be useful for performing toxicological studies involving HDI polyisocyanates.