Ligand-stimulated phosphoinositide hydrolysis activates a bifurcating second messenger system, releasing inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG), which activates protein kinase C (PKC). Yet, in developing cat visual cortex and hippocampus, high levels of [3H]PDBu binding (labelling PKC) appear much earlier than do [3H]IP3 labelled sites. Binding distributions for the two ligands also appear to be complimentary in both brain regions. Moreover, early surgical removal of input to the visual cortex increases [3H]PDBu binding without affecting that of [3H]IP3. Our results suggest that, (1) at certain developmental stages, IP3 and PKC may act individually or complimentarily rather than synergistically in the visual cortex and hippocampus; (2) in neonatal cortex, IP3 metabolites rather than IP3 itself may act as second messengers; (3) although both IP3 receptors and PKC are localized in intracortical cells, their expression is regulated by different mechanisms during development.