Ligand binding to neurotransmitter and hormone receptors which couple to the Gq subclass of GTP-binding protein leads to the activation of phospholipase Cβ (PLCβ) which hydrolyses phosphatidyl-inositol 4,5-bisphosphate, yielding a pair of second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (IP3). The expression of PLCβ1–4 mRNAs was comparatively examined by in situ hybridization in the mouse brain. In adults, PLCβ1 mRNA was expressed predominantly in the telencephalon, including the cerebral cortex, hippocampus, amygdala, lateral septum and olfactory bulb, with little expression in most thalamic nuclei. PLCβ2 mRNA was distributed in the white matter, suggesting its expression in non-neuronal cells, most likely oligodendrocytes. PLCβ3 mRNA was specifically expressed in cerebellar Purkinje cells. The highest levels of PLCβ4 mRNA were detected in Purkinje cells. High levels of PLCβ4 mRNA were also found in the thalamus and medial septum, whereas weak signals were detected in most telencephalic regions, thus showing an expression pattern almost reciprocal to that of PLCβ1 mRNA. During development, such characteristic regional expression of PLCβ1 and PLCβ4 were observed starting in late foetal stages, while specific expression of PLCβ2 and PLCβ3 appeared in early postnatal stages. We conclude that despite the existence of four PLCβ isoforms, only one or two of them is expressed in individual neurons and glial cells. The distinct expression of PLCβs provides a molecular basis for analysing the nature of the specific signal transduction pathway leading to the production of diacylglycerol and IP3 in distinct cell types and in different regions of the brain.