The purpose of these studies was to develop novel methods to investigate the biological fate of inhaled ozone and other oxygen-containing pollutants in animal and human tissues using the heavy isotope of oxygen, oxygen-18 (18O). Methods were developed which facilitated the conversion of tissue oxygen to CO2 and the subsequent trapping of the CO2 so that it could be subjected to isotope-ratio mass spectrometry. The ratios of the various masses of evolved CO2 were used to calculate the 18O content of the original tissues, thus enabling the detection of isotopic enrichments as small as 0.4%. The above procedures were performed by modification of a commercially available elemental analyzer to include effluent columns and trapping devices, development of oxygen isotopic standards, and by derivation of mathematical models for correction of blank and memory effects originating during sample pyrolysis. These techniques were applied with success to the determination of the biological fate of inhaled ozone, and to the measurement of tissue oxidation induced by a model peroxidation initiator, carbon tetrachloride.