We tested the hypothesis that depressed duodenal calcium absorption in the streptozotocin diabetic rat is the consequence of diabetes rather than nephrotoxicity of the diabetogenic agent causing abnormal renal vitamin D metabolism. We treated streptozotocin diabetic rats with insulin and compared their duodenal calcium transport response with that of untreated diabetics and matched controls. Insulin treatment restored depressed calcium transport of diabetics to control levels in in vivo studies and significantly increased calcium transport in vitro. Previous studies showed that even in uncontrolled diabetes the mucosa retains the ability to respond to an end organ stimulus enhancing calcium transport: 1,25-dihydroxycholecalciferol corrects the defect, but vitamin D and 25-hydroxycholecalciferol are ineffective. Since 1,25-dihydroxycholecalciferol is synthesized in the kidney, these findings, in conjunction with the current study, are consistent with the association of experimental diabetes with a renal defect depressing synthesis of 1,25-dihydroxycholecalciferol. Since insulin treatment restores duodenal calcium transport, the renal defects is unlikely to be caused by streptozotocin nephrotoxicity.