We investigated the effects of acute i.p. injections of the Ca2+-dependent K+ channel blocker, apamin, on water maze spatial navigation, Y-maze and passive avoidance behavior in intact and medial septal-lesioned mice. Apamin 0.02, 0.06 or 0.2 mg/kg (i.p.) administered 30 min before or immediately after the training did not affect the performance of intact mice. Apamin 0.02 or 0.06 mg/kg (i.p.) administered immediately after the daily training did not affect the performance of medial septal-lesioned mice. Apamin 0.02 and 0.06 mg/kg (i.p.) administered 30 min before daily training reversed the navigation failure present in medial septal-lesioned mice during the initial and reversal learning stages of the water maze task. Apamin had no effect on the cognitive performance in Y-maze or passive avoidance tests. The results indicate that blockade of Ca2+-dependent K+ channels may facilitate acquisition of spatial navigation performance, but has no effect on consolidation, inhibitory avoidance and spontaneous alternation behavior in mice.