Amyloid β protein (A β), has been reported to be toxic to neurons in vitro. However, the molecular mechanism leading to neuronal death remains unknown. Here we report protective effects of phenothiazines, a class of neuroleptic agent, against A β toxicity in primary cultures of rat cortical neurons and PC12 cells. β(25-35), an active sequence of A β, showed dose-dependent reduction of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye (MTT) reductivty, and chlorpromazine (CPZ), promethazine or trifluoperazine restored it at micromolar concentration. The significant increase in Ca 2 + uptake by chronic treatment of β(25-35) was reduced not only by nimodipine but also by CPZ. These results suggest that phenothiazines attenuate β(25-35) toxicity possibly by reducing of Ca 2 + influx through L-type Ca 2 + channels.