In guinea pig hippocampal slices, 4-aminopyridine (4-AP) in concentrations of 100-500 microM reduced the adaptation of CA3 pyramidal neurons to depolarizing stimuli, resulting in a prolongation of repetitive firing during injection of long-lasting depolarizing currents. Concurrently, there was a decrease in the 'sag' of potential after spike bursts. Furthermore, 4-AP decreased or abolished the hyperpolarizing potential (the afterhyperpolarization) which normally followed repetitive firing of the neurons. The findings suggest that 4-AP could interfere with the Ca2+-activated K+ current in hippocampal CA3 pyramidal neurons.