Abstract In current-clamp recordings with KMeSO 4 electrodes (either whole-cell or intracellular), though tolbutamide (0.5–1 mM) did not change the resting potential, it increased both input resistance (by 12 ± 3.8%) and spontaneous firing, and spikes were evoked by smaller depolarizing pulses. Tolbutamide reduced in a dose-dependent manner both components of post-burst afterhyperpolarizations: IC 50 was 0.15 mM for medium afterhyperpolarizations and 0.33 mM for slow afterhyperpolarizations. In whole-cell recordings under voltage-clamp, 0.5–1 mM tolbutamide depressed slow outward currents by 65 ± 5.3%. The tolbutamide-sensitive current was Ca 2+-dependent — tolbutamide being ineffective in Mn 2+, low Ca 2+-containing medium — though tolbutamide did not significantly depress high voltage-activated Ca 2+ currents. Tolbutamide reduced C-type outward currents by 45 ± 5.9% and M-type current inward relaxations by 41 ± 12.9%, as well as Q-type current inward relaxations by 22 ± 5.7%. Glyburide (10 μM) did not depress afterhyperpolarizations or outward currents, even in recordings with electrodes containing 1 mM guanosine diphosphate. We conclude that the most prominent effects of 0.5–1 mM tolbutamide on CA1 neurons are caused by suppression of Ca 2+- and voltage-dependent outward currents, including I AHP, I C and I M.