The hypothesis that the influx of extracellullar Ca2+ across a damaged plasma membrane is the final common pathway for chemically mediated cell death has stirred considerable controversy and continued interest in the study of subcellular ion shifts as sensitive indicators of hepatotoxicity caused by environmental pollutants. A number of studies have shown that increases in hepatic mitochondrial calcium result from the ingestion of carbon tetrachloride. Quantitative measurement of calcium in subcellular components was accomplished in early studies by using techniques involving whole tissue homogenation and fractionation by centrifugation. In the study x-ray microanalysis of quick-frozen liver tissue, cryo-sectioned for the electron microscope, provided an alternative approach to studying subcellular ion distribution.