The biochemical and pharmacological characteristics of specific binding sites for gastrin-releasing peptide (GRP) were investigated in normal exocrine pancreas and in an azaserine-induced pancreatic carcinoma in the rat, under similar experimental conditions. Cells from both types of tissues contained rapid, reversible, temperature-dependent, and highly specific binding sites for GRP. Scatchard analysis of equilibrium data obtained with normal and tumor plasma membranes indicated a single class of high-affinity sites (KD = 0.42 +/- 0.06 and 0.35 +/- 0.05 nM, respectively), but the number of GRP receptors was significantly different (Bmax = 31 +/- 4.5 and 189 +/- 20 fmol/mg protein, respectively). Binding of 125I-GRP1-27 was sensitive to GTP analogues, suggesting that the GRP receptor is functionally linked to a guanyl regulatory protein; however, the wheat germ agglutinin-agarose purified receptor had lost this G-protein activity. Cross-linking of 125I-GRP1-27 either to normal and neoplastic cells or to crude membranes, solubilized membrane proteins, and partially purified receptors revealed the presence of a specific MW 75-kDa polypeptide. N-Glycanase treatment reduced this apparent MW to about 45 kDa. Together, these data suggest that normal and tumor pancreatic cells contain a specific GRP receptor that is expressed more on malignant pancreatic tissues.