Congenital deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) in humans results in a severe neurogenetic disorder known as the Lesch-Nyhan syndrome. Since little information concerning the precise localization of HPRT in the brain is currently available, we have used in situ hybridization to examine the expression of HPRT mRNA in the mouse brain. The results showed that HPRT mRNA is expressed in many regions of the normal mouse brain, with high levels in most, but not all neurons. In contrast, glial cells did not express detectable levels of HPRT mRNA. No HPRT mRNA was detected in the brains of mutant mice carrying a deletion in the HPRT gene.