The efflux and uptake of [3H]Ca antagonists were studied in isolated rings of rabbit aorta. The efflux of [3H]bepridil occurred from two compartments. The faster (T1/2 = 0.6 min) initial compartment presumably represented efflux from the extracellular space. The slower (T1/2 = 25 min) component probably reflected efflux from the intracellular space. The uptake of [3H]bepridil into the cells occurred at an initial rate of 0.001 pmol/s . cm2, and by 80 min, uptake had reached steady state. Increasing the Ca2+ concentration to four times normal caused a marked decrease in the [3H]bepridil uptake, implying a possible competition between Ca2+ and bepridil. However, decreasing the Ca2+ concentration to one-fourth normal caused a slight decrease in [3H]bepridil uptake. [3H]Verapamil was not appreciably taken up by the tissues (less than 10% of [3H]bepridil uptake) unless the cell membranes were disrupted by digitonin treatment. (Lowering the Ca2+ concentration to one-fourth normal slightly increased. [3H]verapamil uptake.) These data suggest that bepridil can cross the sarcolemma (and therefore may exert some internal effect), whereas verapamil is effectively excluded from the cell interior by the cell membrane.