Computer simulations of the time course of amiloride-sensitive Na+ uptake in renal brush border membranes demonstrated that the presteady state lage and burst phases result from separate reactions in the transport cycle. The best fit to the experimental data was obtained using a model in which a Na+ -induced conformational transition is responsible for the lag phase. An analysis of the time dependence of K+-induced dephosphorylation of Na, K-ATPase revealed that the observed kinetic behavior does not conform to a simple mechanism. The complex behavior is attributed to parallel pathways of ATP hydrolosis arising from enzymes that are post-translationally modified or situated in different microenvironments.