Levels of secretin-like immunoreactivity in the plasma of 50 starved subjects were measured by radioimmunoassay and rose from 18 +/- 3 (S.E.) pg/ml after 12 h, to 103 +/- 12 pg/ml (P less than 0.005) after 36 h. The assay antibodies were found to be specific for a region of secretin located towards the C-terminal residue. Lactoperoxidase was used to label the secretin with 125I and ionexchange chromatography on SP-Sephadex C-25 was used to purify the labelled product. The plasma immunoreactivity was purified by immunoaffinity chromatography on antibody-Sepharose conjugates and characterised by gel-filtration on Sephadex G-50 calibrated with molecular weight markers. After a 12-h fast, 10-20% of the immunoreactivity had a molecular weight of about 12 000, possibly due to precursors of secretin. Most of the remainder was smaller than secretin with molecular weight of less than 3000. This material comprised over 90% of the plasma immunoreactivity after a 36-h fast and may be due to degradation products.