The effect of four drugs considered as cognition enhancers on the amplitude of the population spikes and on the long-term potentiation (LTP) evoked by perforant path stimulation was investigated in rat dentate gyrus in vivo. LTP was characterized by the absolute increase in the amplitude of the population spikes, which were expressed in mV, contrary to the widely used percentage value, because the absolute increase was independent of the pretetanus level, whereas the percentage increase was found to be negatively correlated with it. Intravenous administration of the drugs (piracetam 500 mg/kg, hydergine 2 mg/kg, vinpocetine 0.1 and 5 mg/kg and physostigmine 0.01 and 0.1 mg/kg) did not influence the amplitude of the population spikes itself. Piracetam and hydergine did not have an effect on LTP, while vinpocetine and physostigmine altered LTP in a similar manner. The higher doses of the two latter drugs, administered 5 min before tetanic stimulation, induced a significant potentiation of LTP, whereas a significant inhibition of LTP was obtained when the drugs were administered 30 min before tetanic stimulation. Based on the results obtained from guinea pig hippocampal slices, an LTP-potentiating effect of all compounds tested could have been anticipated, but this was not supported by our data. The apparent contradiction between the in vivo and in vitro results is discussed.