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Complications of visceral leishmaniasis are explained in part by immune complex pathology, particularly nephritis. Using the polyethylene glycol precipitation method, we identified among these complexes a Leishmania infantum circulating antigen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Monoclonal antibodies were produced to specifically detect this antigen. This protein (molecular weight 51 kD) is a cytoplasmic antigen of L. infantum and its synthesis by promastigotes is related to stationary-phase culture. It was present in sera from dogs whose leishmaniasis was associated with nephritis, and it was found in the sera of 30% of human patients with visceral leishmaniasis. It was also detected in the sera of patients with cutaneous leishmaniasis, and it persists in the sera of clinically cured subjects.