The different roles of gastrin and cholecystokinin in the fetus compared to the adult may be reflected in different distribution patterns. Re-expression of these fetal patterns is often seen in tumours of the adult. Using region-specific antisera and chromatography, we have determined the ontogeny of amidated gastrin (G-amide), glycine extended gastrin (G-gly), and cholecystokinin (CCK) in various segments of the colon and compared it to the developmental profile in the duodenum. Fetal sheep aged 80-90, 115-125 and 135-144 days (term is 145 days), 7-14 day lamb, and adult sheep were examined. In the colon, higher concentrations of G-amide (2.8 +/- 0.2 pmol/g) and CCK (11.7 +/- 1.6 pmol/g) were measured in the fetus while G-gly (0.7 +/- 0.1 pmol/g) was higher in the adult compared to other age groups. The calculated G-gly/G-amide ratio was 0.4 in the fetus and 1.4 in the adult while the CCK/G-amide ratios were 5 in the fetus and 13 in the adult. The duodenum of the lamb rather than the fetus contained the highest concentrations of G-amide, G-gly and CCK (40.3 +/- 9.7, 2.0 +/- 0.4, 109.0 +/- 14.3 pmol/g, respectively) and at concentrations exceeding that in the colon. The results demonstrate two major developmentally regulated features. Firstly as the colon matures, there is a gradual switch between the expression of the gastrin and CCK genes and secondly, the processing to G-amide is attenuated. These findings suggest that non-amidated gastrin should be examined for a potential role as a growth factor in colorectal carcinogenesis.