We have applied a sensitive and discriminating electrophoretic technique that distinguishes between fibrinogen, fibrin polymers, fibrinogen degradation products (FDP), and cross-linked fibrin degradation products (XLDP) to evaluate urinary fibrinogen antigen in control subjects and in patients with a variety of renal diseases and after renal allograft transplantation. Although only one of 11 controls showed the trace presence of urinary fibrinogen, 14 of 28 patients with renal disease had urinary fibrinogen antigen, mostly as fibrinogen or fibrin monomer. Thrombin treatment failed to remove fibrinogen from urine, indicating that methods using this step to eliminate clottable protein will overestimate the quantity of urinary fibrinogen and fibrin degradation products. No association was found between the amount or type of antigen and the specific clinical diagnosis or the presence of proteinuria or hematuria, although urinary FDP and XLDP were found only with greater degrees of renal impairment. Fifteen patients were evaluated for 3 weeks after renal transplantation surgery by serial urine and serum electrophoretic analysis. Urinary FDP and XLDP were found significantly more often in the first week after surgery and in association with episodes of acute renal transplant rejection (ARTR) than at other times. This suggests that fibrin deposition and degradation is involved in the pathologic process of ARTR and that identification of specific XLDP and FDP could have diagnostic and prognostic application in such patients.