The hepatic uptake of C-peptide is believed to be negligeable; this, however, is based on indirect evidence. In the present work, C-peptide was measured in four non obese non diabetic men simultaneously in portal blood and bile. Small amounts of C-peptide were found in bile, compared with portal levels; these data are consistent with a minor role of the liver in C-peptide metabolism but represent a direct demonstration of an extraction of the peptide by the liver in man.