We examined the effects of changes in pHo and pHi on currents contributing to the medium and slow afterhyperpolarizations (mIAHP and sIAHP, respectively) in rat CA1 neurons. Reducing pHo from 7.4 to 6.7 inhibited mIAHP and sIAHP whereas increasing pHo to 7.7 augmented mIAHP and, to a greater extent, sIAHP. The ability of changes in pHo to modulate mIAHP reflected changes in the Ca2+-activated K+ current, IAHP, and a Co2+- and XE991-resistant component of mIAHP, but not the muscarine-sensitive current, IM. In the presence of 1 µM TTX and 5 mM TEA, low pHo-evoked reductions in sIAHP were associated with reductions in Ca2+-dependent depolarizing potentials; because neither effect was attenuated when internal H+ buffering power was raised by including 100 mM Tricine in the patch pipette, the actions of reductions in pHo to inhibit sIAHP and, possibly, IAHP in large part appear to reflect a low pHo- dependent decrease in Ca2+ influx. In contrast, the effects of high pHo to augment mIAHP and sIAHP were associated with relatively small increases in Ca2+ potentials but were significantly attenuated by 100 mM internal Tricine, indicating that a rise in pHi consequent upon the rise in pHo was largely responsible. The possibility that changes in pHi could act to modulate mIAHP and sIAHP independent of changes in Ca2+ influx was also suggested by experiments in which pHi was lowered at a constant pHo by the external application of propionate or by the withdrawal of HCO3- from the perfusing medium. Lowering pHi at a constant pHo had little effect on Ca2+ potentials but inhibited mIAHP and, to a greater extent, sIAHP, effects that were attenuated by 100 mM internal Tricine. Together, the results indicate that changes in pHo and pHi modulate mIAHP and sIAHP in rat CA1 neurons and suggest that, depending on the direction of the pHo change, the sensitivities of the underlying currents to changes in Ca2+ influx and/or pHi may contribute to the effects of changes in pHo to modulate mIAHP and sIAHP.