The ratio initial/final urea value is used in urea kinetic formulas. To assess its reliability we employed mass balances and urea clearances to study 15 hemodialysis treatments divided in several parts. The mass balances clearly indicated urea disequilibrium. In the first phases of dialysis, urea extraction, measured by dialysate collection, was lower than the corresponding change in urea pool, whereas in the later phases the opposite occurred. On account of this lack of equilibrium, clearances bases on the Co/Ct ratio (K2) are less reliable than standard clearances derived from total dialysate collection (K1): in the first quarter of dialysis, K2 is greater than K1 (p less than 0.01), while in the 3rd and 4th quarters it is lower. The comparison of clearances in a cumulative way showed a significant fall in K2 (p less than 0.01) while K1 remained stable. From a practical point of view, aberrations induced by non monocompartmental urea behaviour are negligible, and do not invalidate the usefulness of the single-pool Gotch model in clinical practice. However, at least in experimental work, the limits of urea kinetic formulas must be taken into account.