The present study was conducted to evaluate the effect of 2-phenylethynyl-butyltellurium (PEBT), an organotellurium compound, at doses of 5 and 10 mg/kg on memory, employing the step-down inhibitory avoidance task in mice. Moreover, the involvement of glutamate uptake and release in cerebral cortex and hippocampus of mice was investigated. A single oral administration (p.o.) of PEBT at the dose of 10 mg/kg 1 h before training (acquisition), immediately after training (consolidation) or 1 h before the test session (retrieval) of the step-down inhibitory avoidance task increased the step-through latency time in comparison to the control mice. In the open-field test, no significant differences in the number of crossings and rearings were observed among groups. The [3H]glutamate uptake by cerebral cortex and hippocampal slices of mice was significantly inhibited after 1 h of treatment with PEBT. After 24 h of PEBT exposure, only the hippocampal [3H]glutamate uptake was inhibited. The [3H]glutamate release by cerebral cortex and hippocampal synaptosomes of mice was not altered. These results suggest that PEBT improved memory stages (acquisition, consolidation and retrieval) in the step-down inhibitory avoidance task in mice. The improvement of memory by PEBT seems most likely to be mediated through an interaction with the amino acid transporters of the glutamatergic system.