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Locomotor activity and brain catecholamine concentrations following d-amphetamine challenge were evaluated in lead-exposed rats. Sucklings were exposed to lead via its transfer from maternal drinking solutions (0.02% Pb (Ac)2, 109 ppm Pb) to the maternal milk supply. At 21 days of age half of each exposed litter was weaned to the maternal regimen, the remainder to distilled water. Spontaneous locomotor activity and lead in blood were qualified at 21, 30 and 90 days of age. At 90 days of age rats were also challenged with d-amphetamine sulfate (1.0 mg/kg, SC) and their drug-induced activity recorded for a 2 hours period. One week later the same animals received a similar dose of d-amphetamine and were sacrificed at 0, 0.5, 1, 3, 6, 12, 24 and 48 hours post injection for analysis of whole brain dopamine (DA) and norepinephrine (NE). Catecholamine concentrations did not differ between lead-exposed and control rats in the absence of a d-amphetamine challenge. However, over the 48 hr period following drug challenge, lead-exposed rats had lower whole brain steady state levels of NE than control animals. Similar changes were evident for rats exposed to lead continuously and for those exposed to lead only during the 21 day period from birth to weaning. The spontaneous locomotor activity of lead-exposed and control rats was comparable at all ages tested. However, drug-induced activity was greater in lead-exposed animals than controls. This facilitated drug response was statistically greater than that of controls for continuously lead-exposed rats. Those exposed only during the neonatal period showed similar trends.