We investigated the effect of perinatal, low-level lead exposure on [3H]hemicholinium-3 (HC-3) binding in the hippocampus of postnatal rat. Rat pups were maternally lead-exposed from gestational day 16 through postnatal day 28 (PN28). In control animals, the [3H]HC-3 binding sites increased from 7 fmol/mg protein at postnatal day 1 (PN1) to 14 and 35 fmol/mg protein at PN7 and PN14, respectively, and reached adult values of 50 fmol/mg protein, at PN21 and PN28. In lead-exposed litters, the [3H]HC-3 binding was reduced by 30-40% throughout the early postnatal development and remained 40% below control values in PN60 animals, one month after termination of lead exposure. The Pb-induced reduction in HC-3 binding was associated with a similar decrease in ChAT activity and was comparable to the effect of localized lesion of medial septum. Septal cell counts in the lead-exposed PN21 rats indicated a 22% reduction in the number of ChAT-immunoreactive cells in the medial septum/vertical diagonal band (MS/vDB) complex although cell numbers in the horizontal limb of the diagonal band (hDB) were not altered. These results suggest that perinatal, low-level lead exposure results in a reduced density of cholinergic nerve terminals in the hippocampus, either due to impaired development or degeneration of the cholinergic projection neurons in the MS/vDB complex.