Biochemical analysis of muscarinic- and metabotropic-glutamate receptor stimulated phosphoinositide (PI) turnover in rat cortical preparations during the first three weeks of postnatal development indicates the existence of a transiently increased accumulation of labeled inositol polyphosphates during the first postnatal week (Gonzales and Crews, 1985; Dudek et al., 1989). We now report for first time the visualization of those neurons responding with increased PI turnover to glutamatergic or cholinergic-receptor stimulation in rat somatosensory cortex during early postnatal development utilizing a recently described method (Bevilacqua et al, 1994). Three, 7, 10, 14, and 21 d old rats were studied. Carbachol in the presence of lithium stimulates 3H-CMP-PA accumulation throughout the cortex at all ages studied. In comparison labeled neurons responding to t-ACPD in the presence of lithium were located exclusively in layer V at P3 and P7, but were found labeled throughout the cortex at P10. Given that glutamate and cholinergic agonist stimulation are both necessary but not sufficient for cortical plasticity to occur, and that muscarinic and mGluRs stimulation both induce a peak in PI turnover response during the same period of experience-dependent neocortical plasticity, PI derived second messengers signals might be involved in the regulation of the molecular mechanisms of neuronal plasticity. Furthermore, our results show the anatomical correlate of receptor-specific PI turnover activation, and indicate that specific agonist induced PI responses are age, and layer specific.