Ornithine decarboxylase (ODC) is a growth-associated enzyme which is critical for cell growth and transformation. ODC activity follows a specific ontogenetic pattern of activity in distinct brain regions according to their developmental stage. Perturbations in the pattern of ODC activity have been associated with brain damage including arrested cerebral growth. Modulations in the pattern of ODC activity were examined in the hippocampus, neocortex and cerebellum of neonatal rats (PND 3, 6, 9, 15) exposed via the dam to 0.2% lead-acetate (Pb2+ prenatally (gestational day 13 to birth), postnatally (PND 1-15) or perinatally (gestational day 13 to PND 15). Prenatal exposure to Pb2+ perturbed the profile of ODC activity in all three brain regions examined, while postnatal exposure to Pb2+ resulted in prolonged stimulations of ODC activity in the cerebellum. Following prenatal exposure, these effects were manifested as a stimulation of ODC activity in the hippocampus, a repression of activity in the neocortex and a combination of these effects in the cerebellum. Perinatal exposure to Pb2+ transiently modulated the pattern of ODC activity similarly in all three brain regions, in a characteristic manner irrespective of their developmental stage. These Pb(2+)-induced modulations of ODC activity suggest that polyamine-dependent processes may play a significant role in the manifestation of Pb(2+)-induced neurotoxicity dependent upon developmental factors at specific exposure periods.