Based on our previous finding in lung parenchyma of high concentration of the shared epitopes of gp600, a well characterized kidney glycoprotein, we attempted to identify the anatomic site of these epitopes and characterize them biochemically. Affinity-purified polyclonal anti-gp600 antibody was used as the probe. Immunocytochemically in lung on light and electron microscopy the probe reacted exclusively with type II pneumocytes and no other lung cell. The reaction was also demonstrated on freshly isolated and cultured type II pneumocytes. Both approaches showed the reaction to localize on the cell membrane of type II pneumocytes. Immunoprecipitation of radiolabeled type II pneumocyte cell membranes identified two 270- to 290-kDa polypeptides as the reactive proteins. We conclude that the reactive epitopes for anti-gp600 in lung parenchyma are exclusively localized on type II pneumocytes and have a Mr of approximately 270 to 290 kDa and that anti-gp600 may be used as a specific immunologic marker for the type II pneumocytes. Finally, it is possible that the differences in the molecular forms of the cross-reactive proteins in lung and kidney identified in this report are the reason for the known non-nephritogenicity of rat lung for the induction of Heymann nephritis in rat.