The normal range for whole blood serotonin levels in chronic renal failure patients has not been defined. As serotonin may be implicated in platelet abnormalities, hypo- and hypertension and itch in dialysis patients, serotonin whole blood levels were measured in a group of patients with chronic renal failure and/or who were dialysis dependent. The levels were elevated in 12 patients with moderate (mean serum creatinine 335 ± 54 µmol/l) chronic renal failure (270 ± 46 µg/l) compared to 11 normals (163 ± 17 µg/l, p < 0.05; quoted normal range < 300 µg/l) but did not correlate with serum creatinine levels. There was a marked elevation in serotonin levels in dialyzed patients, including those on hemodialysis (polysulfone, n = 6, 747 ± 234 µg/l; cuprophane membranes, n = 6, 708 ± 198 µg/l), hemodiafiltration (n = 12, 695 ± 130 µg/l) and especially peritoneal dialysis (n = 6, 1,148 ± 162 µg/l). All results were significant (p < 0.01) compared to normals and compared to the nondialyzed group (p < 0.05). The level of serotonin decreased during hemodialysis regardless of the membrane used. There was no positive correlation of serotonin levels with pruritus or hypertension, although there was a negative correlation with systolic blood pressure. The reference range for serotonin whole blood levels needs to be broadened when considering dia