Cholecystokinin (CCK)-8 and human gastrin I (gastrin) were found to be almost equipotent in displacing the specific binding of not only 125I-CCK-8 but also 125I-gastrin to both ECL carcinoid tumor and parietal cell membranes of Mastomys natalensis. These binding specificities of the native gastrin receptors for CCK-8 and gastrin were identical to that of the cloned gastrin receptor from the ECL carcinoid tumor expressed on CHO-K1 cells. In contrast, CCK-8 was approximately 10-20 times as potent as gastrin in inhibiting the binding of the two radioligands to the Mastomys brain membrane. However, the nucleotide sequences of RT-PCR products of mRNAs extracted from not only the isolated parietal cells but also the brain were identical to that of the gastrin receptor cDNA from the ECL carcinoid tumor. Thus, the gastrin receptors on the parietal cells and the brain appear to be encoded by the same gene as those on the ECL carcinoid tumor in Mastomys. The reason for the difference in binding characteristics between the cloned gastrin receptor and the native gastrin/CCK-B receptor in the brain remains to be elucidated.