We examined the effect of chronic exposure to lead (Pb(2+)) on protein kinase C (PKC) in 50-day-old rat hippocampus. Cytosolic and membrane fractions of hippocampus from Pb(2+)-exposed rats showed reduced expression of PKC gamma protein. In contrast, a significant elevation of PKC gamma mRNA was observed in pyramidal and dentate granule cell layers. Protein expression of alpha, beta I, beta II and epsilon isoenzymes were unchanged in Pb(2+)-exposed rats, as was [(3)H]phorbol 12,13 dibutyrate (PDBu) binding in tissue slices. Differences were not observed in Ca(2+)-dependent or -independent PKC activity, or in PKC-specific back-phosphorylation of hippocampal homogenates from Pb(2+)-exposed rats. Reduced subcellular levels of PKC gamma in Pb(2+)-exposed rats suggest that signal transduction in the hippocampus may be selectively altered and may be important in manifesting Pb(2+)-induced impairments of synaptic plasticity, learning and memory.