Transcobalamin (TC) has been cloned and used for studying its gene expression in the rat. TC mRNA is distributed widely in adult rat tissues, but at different levels (Kidney > liver>lung>yolk sac>intestine>heart>brain>spleen>muscle). TC mRNA levels were 4-fold higher in the jejunum and ileum compared to its levels in the duodenum. During postnatal development, TC mRNA levels in the ileum declined 4-fold from day 4 to day 12, but increased by 5-fold between day 12 to day 24. In contrast, TC mRNA levels increased by 2.5-fold in the kidney from day 4 to day 12 and then declined by 2-fold by day 24. Adrenalectomy of adult rats resulted in a 4-fold decline in ileal levels of TC mRNA and a 50% decline in the ileal mucosal formation of TC-57[Co]Cbl following oral administration of 57[Co]Cbl complexed to gastric intrinsic factor (IF). Cortisone treatment reversed these changes noted in the ileum. In contrast to ileum, kidney TC mRNA levels were not altered significantly in adrenalectomized rats before and after cortisone treatment. Taken together, this study has provided evidence for regulation of TC gene expression in the rat kidney and intestine during their postnatal development and cortisone selectively regulates ileal but not kidney TC mRNA levels.