Energy dispersive X-ray microanalysis was employed to determine the intracellular electrolyte concentrations in various epithelial tissues. Analyses of the changes in the intracellular electrolyte concentrations during different functional states provided new insights into the mechanisms involved in transepithelial ion transport. Results obtained on the Na transporting frog skin epithelium confirmed the two-barrier concept of transepithelial Na transport involving a passive Na uptake and an active Na extrusion. The Na transport compartment comprises all living epithelial cell layers, only the outer cornified cells, the mitochondria-rich cells and gland cells being exceptions. Na influx across the outer barrier can be inhibited by amiloride or stimulated by novobiocin or vasopressin. In the Cl-secreting frog cornea the electrolyte concentrations in the various epithelial cell layers and cell types were almost identical, indicating that the epithelium forms a functional syncytium with regard to ion transport. Under virtually all experimental conditions the Cl concentration was found to be higher than the expected equilibrium values, favouring a passive exit from the cells towards the tear side. The results are consistent with the existence of a furosemide-sensitive coupled NaCl uptake process at the inner-facing cell membranes. In the rat kidney after K depletion a fall in cellular K by about 20% was observed both in proximal and distal tubular cells. Simultaneously a rise in the intracellular Na concentration was detected which, however, was insufficient to balance the loss in K. No significant differences could be detected between the various epithelial cell types which are thought to be involved in either K reabsorption or secretion. It is concluded that the fall in cellular K is not sufficient to explain the marked reduction in urinary K excretion during K depletion.