Increases in transepithelial solute permeability were elicited in the frog skin with external hypertonic urea, theophylline, and vasopressin (ADH). In external hypertonic urea, which is known to increase the permeability of the extracellular (paracellular) pathway, the unidirectional transepithelial fluxes of Na (passive), K, C1, and urea increased substantially while preserving a linear relationship to each other. The same linear relationship was also observed for the passive Na and urea fluxes in regular Ringer and under stimulation with ADH or I0 mM theophylline, indicating that their permeation pathway was extracellular. A linear relationship between C1 and urea fluxes could be demonstrated if the skins were separated according to their open circuit potentials; parallel lines were obtained with increasing intercepts on the CI axis as the open circuit potential decreased. The slopes of the C1 vs. urea lines were not different from that obtained in external hypertonic urea, indicating that this relationship described the extracellular movement of C1. The intercept on the ordinate was interpreted as the contribution from the transcellular CI movement. In the presence of 0.5 mM theophylline or 20 mU/ml of ADH, mainly the transcellular movement of CI increased, whereas 10 mM theophylline caused increases in both transcellular and extracellular C1 fluxes. These and other data were interpreted in terms of a possible intracellular control of the theophylline-induced increase in extracellular fluxes. The changes in passive solute permeability were shown to be independent of active transport. The responses of the active transport system, the transcellular and paracellular pathways to theophylline and ADH could be explained in terms of the different resulting concentrations of cyclic 5 t .Y-AMP produced by each of these substances in the tissue.