The effect of intracerebroventricular i.c.v. injection of A_25-35 and/or intraperitoneal i.p.) application of the L-type calcium channel (VDCC) blockers verapamil or diltiazem were examined in vivo. In order to by-pass possible systemic actions of these agents their effects on LTP in the CA1 region of the in vitro hippocampal slice preparation were also examined. Application of A_25-35 (10nmol 5µ1, i.c.v.) significantly impaired LTP in vivo, as did i.p. injection of verapamil (1 or 10mg/kg) or diltiazem (1mg or 10mg/kg). In the in vitro slice preparation, LTP was also depressed by prior application of either A_25-35 (500nmol), verapamil (20µM) or diltiazem (50µM). Combined application of A_25-35 and verapamil in either the in vivo or in vitro preparation resulted in a significant reversal of the LTP depression observed in the presence of either agent alone. Co-application of diltiazem and A_25-35 however failed to attenuate the depression of LTP observed in the presence of either agent alone in vivo or in vitro. Since LTP is a cellular correlate of memory, and A is known to be involved in Alzheimers disease (AD) these results indicate that verapamil, a phenylalkylamine may be useful in the treatment of cognitive deficits associated with AD.