Proglucagon mRNA transcripts are transcribed in the pancreas, bowel, and brain, after which posttranslational processing results in the liberation of a different profile of biologically active peptides in each tissue. The receptors for two of these peptides, glucagon and glucagon-like peptide-1 (GLP-1), have recently been identified, but only limited information is available concerning the tissue- and age-specific distribution of these receptors in vivo. We have investigated the expression of these receptors in the mouse using a combination of Northern blot analysis and reverse transcription-polymerase chain reaction. DNA sequence analysis of a partial mouse glucagon receptor cDNA demonstrated a high degree of sequence conservation across rodent species. Glucagon receptor mRNA transcripts were detectable by Northern blotting in poly(A)+ RNA from liver and kidney. Reverse transcription-polymerase chain reaction also detected glucagon receptor mRNA transcripts in both fetal and adult pancreas and lung, jejunum, and ileum, but not in the large intestine. In contrast, mRNA transcripts for the GLP-1 receptor were detected in both small and large intestine as well as in pancreas, liver, lung, and kidney. Both glucagon and GLP-1 receptor mRNA transcripts were identified in different regions of the fetal and adult mouse brain, but the relative levels of GLP-1 receptor mRNA transcripts were much greater in the central nervous system. Furthermore, regulation of the GLP-1 receptor (but not the glucagon receptor) gene in the brain resembled the pattern of region-specific gene expression recently defined for the mouse proglucagon gene. Taken together, these studies define novel sites for both glucagon and GLP-1 receptor gene expression in the mouse and suggest that different regulatory mechanisms have evolved for tissue-specific and developmental control of receptor gene expression.