SUMMARY1. Data on the transport of L-leucine into human erythrocytes at 250 C shows (a) that the carrier re-orientation process is rate determining, (b) that the binding of leucine to the carrier increases the rate of carrier re-orientation and (c) that the carrier is, at equilibrium, about equally distributed between the membrane surfaces at 250 C.2. These conclusions are reached through a new kinetic analysis of a simple carrier system, which involves no prior assumptions about the relative magnitudes of the rate constants, yet leads to usable kinetic equations. These equations allow the determination of the rate determining step, the calculation of the effect of bound substrate on the rate of carrier re-orientation and, in some cases, an estimate to be made of the equilibrium distribution of the carrier between the inner and outer membrane surfaces. rNTRODUCTION The transport of glucose, and, to a small extent, amino acids into the human erythrocyte has been used in establishing the basis of the present theory ofcarrier-mediated transport (reviewed, for example, by Stein, 1967). However, although complete kinetic schemes have been derived for a range of possible carrier mechanisms (Jacquez, 1961), these have always been simplified by a number of critical assumptions before being applied to experimental data. These assumptions have usually been concerned with the nature of the rate-determining step, and with the symmetry of the carrier with regard to the inner and outer surfaces of the membrane. Consequently, no definite information is available on these important features of the mechanism, and the conclusions which have been drawn are in some degree dependent on the validity of the original assumptions. In this paper, a new form of the kinetic equations for the general case is