Previous measurements of elemental concentrations in liver mitochondria have generally required homogenation and fractionation of liver tissue, a procedure in which it is difficult to rule out ion movement between subcellular units. New techniques involving cryo-ultramicrotomy of rapidly frozen tissue, high resolution scanning transmission electron microscopy and X-ray microanalysis were used to measure those elements in rat liver mitochondria reported to have changed following oral administration of carbon tetrachloride (CCl4). Increases in liver mitochondrial calcium were found 24 hours following intoxication by CCl4. Significant early (2 hours) mitochondrial increases in potassium and phosphorus were found following administration of CCl4. The electron microscope technique using quick frozen samples promises to allow measurement of intracellular ionic concentrations under virtually lifelike conditions.