The purpose of this study was to investigate the influence of different adenosine triphosphate (ATP) concentrations (ranging from 400 nM to 250 microM) on hippocampal potentials recorded from pyramidal neurons. ATP applied at a concentration of 400 nM induced a 100% increase in the size of the population spike (potentiation). The potential started to increase 30-60 s after ATP application, reached a maximum after 20 min, and remained potentiated for longer than 1.5 h. Washing the slices with fresh Ringer solution did not reverse the effect. ATP applied at a concentration of 50-150 microM, temporarily depressed the potential. This depression, however, was transient, as the potential gradually recovered by itself and reached a value higher than that observed before ATP application. ATP applied at the concentration of 250 microM caused a long-lasting depression of the potential. The potential was not restored by washing the slices, but recovered after addition of 0.7 microM 3,4-diaminopyridine. These data show a concentration-dependent mode of ATP action on hippocampal neurons and suggest a role for ATP in regulating synaptic efficiency.