The effects of aniracetam, a nootropic drug, and midazolam, which produces amnesia, on the long-term potentiation (LTP) of population spikes was investigated using hippocampal slices (CA3 area) from the guinea pig. Aniracetam at concentrations of 10(-7) and 10(-8) M, but not at 10(-6) M, significantly augmented LTP. On the other hand, midazolam (10(-9) M) significantly suppressed LTP. The suppressive effect was antagonized by Ro 15-1788 (10(-8) M). Both drugs did not affect the population spikes in the absence of tetanic stimulation at those concentrations. It was suggested that in vitro application of LTP is a feasible model system for evaluating the nootropic activity of drugs.