Electrophysiological characteristics of transepithelial Cl-specific conductance (gCl) and intracellular element concentrations were analyzed in frog skins before and during voltage perturbation to serosa +100 mV, both under control conditions and after mucosal application of procaine. Under control conditions, gCl was often minimal and almost insensitive to voltage perturbation. Procaine stimulated gCl in many cases considerably and further activation resulted then from voltage perturbation. Microelectrode determinations indicated that conductive pathways parallel to the principal cells account for the procaine-induced increase in gCl. The responses in gCl were not related to the density of mitochondria-rich (MR) cells. Electron microprobe analysis of intracellular electrolyte concentrations showed that procaine increased the Cl content of MR cells significantly. Gain of Cl was primarily due to uptake across the basolateral membrane, as indicated by the small accumulation of Br after unilateral mucosal application. Voltage perturbation to serosa +100 mV in the presence of Br on the mucosal side led in procaine-stimulated tissues to an increase of the ratio of Br/Cl content in the majority of MR cells. It was much less than predicted for conductive transcellular anion transport. Also, intracellular Cl concentrations of MR cells were far above those expected for a highly Cl-permeable basolateral membrane. The data, although indicating finite Cl/Br transport across MR cells, are incompatible with the idea that the voltage-activated conductive Cl transport occurs though these cells. Alternatively, we suggest passage across highly Cl-specific sites of a paracellular pathway.