Tubuloreticular inclusions (TRI) and cylindrical confronting cisternae (CCC) are present in cells of patients with the acquired immunodeficiency syndrome (AIDS) and have also been detected in the kidneys of individuals with AIDS and heavy proteinuria. We examined renal biopsy tissue from 13 patients with proteinuria and/or renal insufficiency. At the time of biopsy, two of the patients had AIDS (group A), four had AIDS-related complex (ARC) (group B), and seven presented without any clinical signs or symptoms characteristic of AIDS or ARC. These seven had risk factors for AIDS, and systemic lupus erythematosus (SLE) was excluded in all. Abundant TRI were present in the renal endothelial and fibroblastic interstitial cells in all patients from group A and B and in four patients who had no evidence for AIDS or ARC at the time of biopsy (group C). These individuals were followed, and all developed AIDS within a period of 3 to 14 months. CCC were detected in two of two patients in group A, one of four in group B, and one of four in group C. TRI and CCC were not present in the renal tissue of the remaining three patients; they did not develop ARC or AIDS over a prolonged observation period. Our findings suggest that TRI and TRF are ultrastructural markers for human immunodeficiency virus (HIV) associated nephropathy and can be seen before AIDS has manifested itself. These structures may be of predictive value for the future development of AIDS in patients presenting with apparent idiopathic renal disease.