Lead toxicity in the central nervous system seems to be partially related to specific effects of the metal on calcium metabolism and in particular on calcium transport. On this line, the present study investigates the characteristics of [3H]nitrendipine binding to several rat brain regions after in vitro lead addition or after in vivo chronic exposure to this metal. In vivo a lead induced increase in [3H]nitrendipine binding, Bmax, is observed in cerebral cortex and striatum while the binding is unmodified in hippocampus. The in vitro studies are in agreement with in vivo data; lead addition stimulates the binding in synaptic membranes prepared from cortex and striatum but not from hippocampus where the binding is slightly inhibited. The data suggest that lead interferes with neuronal calcium channels in an area-selective manner.