This study on the effect of verapamil on the Na+-dependent Ca2+ uptake system (Na+-Ca2+ exchanger) of synaptic plasma membrane (SPM) vesicles showed that verapamil inhibited the Na+-dependent Ca2+ uptake in a dose dependent manner. A 50% inhibition was obtained with 175 microM verapamil. Calcium uptake in SPM vesicles is dependent on the Na+ gradient across the membrane and on the membrane potential. Both components of the Ca2+ uptake system were inhibited by verapamil. Na+-coupled GABA uptake in SPM vesicles was also inhibited by verapamil in a similar dose-dependent fashion. It seems therefore that verapamil inhibits Na+ gradient driven processes in synaptic plasma membrane vesicles.