Antagonism of NMDA-mediated transmission by MK-801 has been shown to block long-term potentiation (LTP) in vitro and delay electrical kindling of the amygdala. The experiment sought to examine the relationship between synaptic potentiation of the perforant path-granule cell synapse and development of perforant path kindling. MK-801 (0.1 and 1.0 mg/kg) blocked induction of LTP of the perforant path in the unanesthetized animal measured 24 h after train delivery. The 1.0 mg/kg dosage also increased afterdischarge (AD) thresholds, delayed kindling development from daily stimulation of the perforant path (x = 8.82 + or - and 22.9 + or - 3.66 sessions to the first stage 5 seizure), and increased AD durations. Kindling produced a significant potentiation of the EPSP (47%) and population spike (49%) after the first evoked AD in control animals. No significant enhancement of either component of the field potential was observed in MD-801-treated animals. Animals treated with this dosage of MD-801, did, however, kindle in the absence of potentiation at this synapse. It was concluded that although NMDA-mediated potentiation may facilitate kindling, synaptic potentiation does not appear to be a critical requirement for kindling to develop. (Copyright (c) 1990 Elsevier Science Publishers B.V.)