We present the cases of two patients with short-bowel syndrome who failed to achieve therapeutic cyclosporine serum concentrations on oral drug but were successful on intravenous administration. One patient received cyclosporine after renal transplantation for renal failure secondary to enteric oxalosis; the second received cyclosporine for active Crohn's disease. The rapid bowel transit time was the critical factor in limiting cyclosporine absorption in both cases. In studying oral and intravenous pharmacokinetic profiles, we support a zero-order kinetic model for oral cyclosporine absorption.