Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Previous studies have demonstrated that chronic lead exposure could impair the induction and maintenance of long-term potentiation induced by high-frequency stimulation (HFS-LTP). In area CA1 of rat hippocampus, long-term potentiation could also be induced following temporary replacement of 10 mM 2-deoxy-d-glucose (2-DG) for 10 mM glucose in the normal perfusate (artificial cerebrospinal fluid). The present study was carried out to investigate whether chronic lead exposure affected long-term potentiation induced by 2-DG (2-DG-LTP). Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams whose drinking water contained 0.2% lead acetate. Field excitatory postsynaptic potentials (EPSPs) in area CA1 of hippocampus were recorded on postnatal days 25-30. 2-DG application was followed by an increase in EPSP slopes in a time-course-dependent manner in both control and lead-exposed rats, while the amplitude of 2-DG-LTP in the lead-exposed rats (225.9+/-19.0%, n=12) was significantly greater than that in controls (155.2+/-9.8%, n=12). In contrast to the effects of lead exposure on 2-DG-LTP, the amplitude of HFS-LTP in the lead-exposed rats (121.5+/-13.7%, n=12) was significantly less than that in controls (183.9+/-18.6%, n=12). These results indicate that chronic lead exposure had opposite effects on the two types of LTP induced by HFS and 2-DG. This would suggest that the effects of lead on HFS-LTP and 2-DG-LTP are the result of different sites of lead toxicity.