Our studies suggest that treatments, such as kindling and exposure to ethanol in utero, which produce irreversible pathological changes in brain function also selectively alter neuronal responses to NMDA. We have identified increases in agonist potency, which may result from enhanced NMDA receptor expression, as well as both positive and negative modifications of Mg2+ regulation. There is no proof as yet that NMDA receptor plasticity accounts for the kindling phenomenon, for the cognitive deficits associated with fetal exposure to ethanol or for developmental events. However, all the effects we obtained are in the appropriate direction. The same functional parameters altered by kindling and prenatal exposure to ethanol are also modified during the normal development of the brain. It is tempting to speculate that these pathological stimuli produce their effects through the same mechanisms that would normally be activated by developmental signals.