In order to elucidate some conflicting data reported in the literature the diffusion kinetics between red blood cells (RBC) and plasma during dialysis were studied for urea, creatinine and uric acid. Several complementary studies were performed. According to our results urea diffuses very rapidly from RBC to plasma and is almost at equilibrium at the dialyser outlet; thus the extraction of urea during dialysis is from both plasma and RBC. On the other hand creatinine and uric acid hardly diffuse at all from RBC to plasma during blood transit through the hemodialyser and these solutes are thus extracted mainly from plasma. As a consequence an important in-vitro equilibration process occurs for both solutes in blood drawn at the dialyser outlet; the equilibration rate is greatly temperature-dependent and to achieve complete equilibrium at room temperature, up to 6 to 12 hours were needed for creatinine and 2 to 3 hours for uric acid. Moreover, in the case of creatinine, but not for uric acid, a RBC/plasma disequilibrium was also found in blood drawn at the dialyser inlet; this finding is in contrast with previous reports and suggests that with high-efficiency dialysis modalities the interval between two successive RBC transits through the dialyser may be insufficient for complete equilibration of slowly equilibrating solutes. The clinical implications of these findings with respect to the in-vivo dialyser performance and clearance determinations are discussed.