The lung is the primary target organ of airborne heavy metal-induced toxicity. The aims of this study were to investigate differential acute lung cytotoxicity caused by heavy metals using a primary culture of alveolar type II cells and to establish an in vitro assessment model of lung toxicity. The cytotoxicity of heavy metals was determined by measuring the lactate dehydrogenase release and (51)chromium release from lyzed cells. With respect to the LC(50) values, drug concentrations causing a 50% loss in cell viability, the mean value of Hg was 110 microM and that of Cd was 220 to 250 microM. Cytotoxicity was graded high for Hg and Cd, moderate for Pb and Ni, and negligible for Mn. Additional morphological observations of cell membrane integrity by scanning electron microscopy were compatible with the results of biochemical measurements. In conclusion, we have presented an in vitro assessment model of lung toxicity, which can be used effectively to assess the differential effects of heavy metals on alveolar type II cells. The findings suggests that the potential mechanisms of cytotoxicity are dependent on both the nature and the concentration of the metals.