The respiratory tract is one of the major routes of exposure to noxious agents as well as pathogenic particles such as viruses. Natural killer (NK) activity is an important first line of defense to virally infected cells as well as neoplasms, and testing the effects of exposure to toxic compounds on this activity is therefore of importance for the understanding of the immunatoxic potential of the compound. Lymphoid cell suspensions, obtained after enzymatic dispersion of rat lungs and purification over nylon wool calumns showed in vitro natural killer activity towards YAC-lymphoma cells. Validation of the test vich well known NK-activity stimulators as Bacillus Calmette Guerin (BCC), interleukin-2 (IL-2), interferon (IFN) and inhibitors like anti-asiala GM1 antibody confirmed the reliability of the test as an assay for detecting NK-activity in rat lungs. Using this assay, we tested the effects of hexachlorabenzene (HCB), bis(tri-n-buty1tin)oxide (TBTO) and ozone on the NK-activity. Oral exposure to HCB in concentrations of 150 and 450 mg/kg food for six weeks suppressed the NK-activity in rat lungs. This was also true for six weeks of oral exposure of rats to 20 and 80 mg TBTO/kg food, but to a lesser extent. Inhalatory exposure to ozone for 7 days at 0.4-0.8 mg/m* resulted in stimulation, and at 1.6 mg 03/m in suppression of NK-activity. In summary we have developed a reliable method to measure the effects of (toxic) substances on the NK-activity in lungs.