The potency of some competitive antagonists of N-methyl-D-aspartate (NMDA) to antagonize audiogenic seizures was evaluated in genetically epilepsy-prone rats following intraperitoneal or oral administration. The anticonvulsant effects were evaluated on seizures evoked by auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a perspex dome. Sixty and hundred-twenty minutes after intraperitoneal or 120 min after oral administration all compounds showed antiseizure activity with ED50 against clonus ranging from 11.6 to 384 mumol/kg after intraperitoneal and higher doses after oral administration. DL-(E)-2-Amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) and its carboxyethylester (CGP 39551) and 3-((+/-)-2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (CPPene), were the most potent compounds when administered intraperitoneally and orally. 3-((+/-)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid ((-)-CPP) and (+)-CPP showed minor potency as anticonvulsants and 2-amino-7-phosphonoheptanoic acid (2AP7) was the least potent. Following oral treatment, the duration of action of CPPene was about 8 h, while CGP 39551 still protected against audiogenic seizures after 16 h. All compounds were anticonvulsant at doses below those at which overt behavioural side-effects were apparent. CPPene and (+/-)-CPP showed the best therapeutic index among the NMDA receptor antagonists studied. Since some of these compounds showed anticonvulsant properties after oral administration, potential use of these or other selective NMDA antagonists for antiepileptic therapy in man is suggested.