We investigated the effect of tetrahydroaminoacridine, a cholinesterase inhibitor and d-cycloserine (a partial glycine-B agonist of the NMDA receptor complex) on the defect of water maze spatial navigation in rats induced by aging. Tetrahydroaminoacridine (3 mg/kg, i.p.) or d-cycloserine (10 mg/kg, i.p.) enhanced acquisition of the water maze task. A combination of subthreshold doses of tetrahydroaminoacridine (1 mg/kg) and d-cycloserine (3 mg/kg) improved water maze acquisition, but a combination of lower subthreshold doses (tetrahydroaminoacridine 0.3 mg/kg+d-cycloserine 1 mg/kg) was ineffective. Consolidation in water maze test was not improved by tetrahydroaminoacridine (3 mg/kg) and/or d-cycloserine (10 mg/kg). The results suggest that tetrahydroaminoacridine and d-cycloserine synergistically enhance acquisition of spatial navigation in aged rats.