The levels of secreted platelet antigen (LA-PF4/beta TG) were measured by radioimmunoassay in samples of PPP obtained from human blood collected on EDTA and inhibitors of platelet release reaction. These levels in plasma of 17 normal individuals, 18 nondialyzed patients with chronic renal failure, and nine patients on hemodialysis were 31.9 +/- 2.8 ng/ml, 135.1 +/- 21.4, and 291.8 +/- 26.3, respectively. No significant differences were observed in platelet counts and in the levels of this antigen in PRP of these three groups of individuals. The levels of PF4 in PPP of eight normal individuals and in plasma of seven patients with chronic renal failure were 7.41 +/- 0.67 and 7.53 +/- 1.11 ng/ml, respectively. During processing of blood samples in the absence of platelet release inhibitors, platelets of patients with chronic renal failure released less LA-PF4/beta TG antigen than did normal platelets. The mean levels of LA-PF4/beta TG antigen excreted in urine of six normal individuals and 10 patients with chronic renal failure were 57.75 and 1461.5 ng/100 mg of creatinine per day, respectively. After 3 hr hemodialysis, LA-PF4/beta TG antigen levels in PPP increased from 291.8 +/- 26.3 ng/ml to 505.3 +/- 87.3. By contrast, this antigen in three patients with successful kidney transplants rapidly returned to levels close to normal following graft function. Immunoreactive material from pooled urine of patients with chronic renal failure was isolated by isoelectric focusing. This material focused at pH 10.0 to 10.8 and induced DNA biosynthesis in 3(3 swiss cells, indicating its similarity to PBP. It is proposed that elevation of LA-PF4/beta TG antigen observed in plasma of patients with chronic renal failure resulted from the impaired handling of this protein by the kidney.