We measured and characterized the proglucagon (PG) products in plasma obtained from nine uremic patients and six control subjects in the fasting state. The concentrations of PG products measured by direct RIAs were significantly higher in the uremic patients than in the normal subjects; the concentration of total glucagon immunoreactivity in plasma was 209 +/- 20 vs. 70 +/- 11 pmol/L, the glucagon-like peptide-1 immunoreactivity was 154 +/- 33 vs. 41 +/- 13 pmol/L, and the concentration of pancreatic-type glucagon immunoreactivity was 53 +/- 6 vs. 30 +/- 7 pmol/L. By chromatography, the predominating PG products in both uremic and normal plasma were shown to be glicentin [corresponding to PG-(1-69)] and the major PG fragment [presumably corresponding to PG-(72-158)]. In addition, glucagon-like peptide-1 [presumably corresponding to PG-(72-107) amide] was a major product in uremic plasma. Our results suggest that the kidneys play an important role in the removal from plasma of these products of PG.