Previous work has shown that use of hypertonic peritoneal dialysis fluid (7% glucose) results in ultrafiltration and enhanced urea transfer across the peritoneal membrane. Simultaneous creatinine studies showed a similar enhancement with hypertonic fluid which persisted in lesser degree during subsequent isotonic exchanges. The mechanism of solvent drag has been shown to contribute significantly to the increased urea removal with ultrafiltration. In the present study, the role of altered diffusive permeability of the peritoneal membrane as suggested by the creatinine data was evaluated as a possible additional mechanism. Hypertonic exchanges were bracketed by isotonic (1.5% glucose) exchanges during 11 studies in four patients. During six other studies in four patients, isotonic exchanges only were performed. A mathematical model for peritoneal solute transport by diffusion was developed and a method to distinguish alterations in peritoneal membrane permeability from changes in membrane area proposed. The method incorporates the determination and comparison of transport characteristics for two test solutes of widely different molecular weights. Alterations in inulin and urea transperitoneal transport characteristics in the above studies indicate a significant increase in membrane permeability after exposure to hypertonic solutions that persists during subsequent isotonic exchanges. Varying patterns of membrane area and permeability changes occurred during repeated exposure to only isotonic exchanges. The findings are discussed in regard to recent concepts of passive transcapillary transport.