The bidirectional transport of calcium in rat liver was studied using slices labeled with Ca 47 in a closed two compartment system. Steady-state conditions were observed with influx and efflux transfer coefficients of 0.070 and 0.018 per minute, respectively. The rapidly exchanging cell fraction of calcium existed at a concentration three times higher than the average cell concentration of calcium and occupied cell loci comprising less than 25% of the cell mass, suggesting that calcium associated with the cell membranes, nuclei, and mitochondria participated in the rapidly exchanging fraction. At pH 7.4 and 377deg;C, the influx transfer coefficient was 25% above the steady-state condition and accumulation of calcium by the slices occurred. Studies of the effects of varied physical and chemical conditions revealed that the influx transfer coefficient was increased by elevated pH, strontium, certain metabolic inhibitors, and 2 m M concentrations of cyclic adenosinemonophosphate and adenosinetriphosphate. The influx transfer coefficient was decreased by reduced temperature, decreased pH, magnesium, and 10 m M adenosinetriphosphate. The efflux transfer coefficient was increased by elevated pH, strontium, iodoacetate, and adenosinetriphosphate, and was decreased by reduced temperature and by N -ethylmaleimide. These data support the thesis that cell transport of calcium is accomplished by the attachment of calcium atoms to the cell surface and transport through the plasma membrane bound to either specific carriers or to membrane constituents. Conditions which change the affinities, capacities, and mobilities of plasma membrane ligands that bind calcium or cause extracellular chelation of calcium are capable of altering the rate of calcium transport.