Gastrointestinal epithelial cell proliferation is stimulated during lactation in the rat. Serum gastrin levels and food intake are also increased during lactation. We investigated the role of gastrin and food intake as possible mediators of duodenal mucosal growth during the first 15 days of lactation. As the lactation period progressed, significant increases in the following crypt properties were noted: 1) crypt length; 2) cells/crypt; 3) labeling index; and 4) dimensions of the proliferative zone. Maternal serum gastrin levels rose abruptly by the first day of birth and remained elevated throughout lactation. The increases in crypt cell proliferation significantly correlated with food intake but not with serum gastrin levels during lactation. Mucosal mass and villus-crypt dimensions were also significantly increased above virgin levels in lactating antrectomized rats. These results suggest that the increase in duodenal growth during lactation most probably is not mediated by postpartum hypergastrinemia and that the increase in cell proliferation may be a direct response to an enhancement in food intake.