We have carried out high performance liquid chromatographic analysis of serum and ultrafiltrate of blood obtained from uremic patients and normal subjects to elucidate the presence of medium-sized peptides unique to uremia. Many fluorescamine-positive substances, excluding amino acids and guanidine compounds, were increased in uremic serum compared with normal serum. At the 0.5–1.0 pmol/ml serum level, several peaks were unique to uremia. The retention time, fluorescamine reactivity, molecular weight distribution and the result of enzymatic digestion revealed that these peaks are peptidic substance