Changes in membrane integrity have been implicated as a contributing factor in the aging process. We have examined the relative stability of synaptosomal membranes from young and aged mice, in response to chemically induced damage. The basal characteristics of the resting synaptosomes prepared from mice of either age were indistinguishable, as judged by intracellular levels of ionic calcium and by efflux of the fluorescent probe employed, fura-2. However, the response of isolated nerve endings to the presence of a neurotoxic agent, the insecticide chlordecone, was markedly different. Exposure to this chemical invariably elevated free calcium and increased the rate of leakage of fura-2 into the extracellular space. These effects were much more pronounced in preparations derived from aged animals. The implication of these findings is that neural membranes of aged animals are more susceptible to malfunction induced by xenobiotic agents and are less able to maintain homeostasis under such circumstances.