A 45-year-old woman receiving hydralazine and hydrochlorothiazide therapy was found to have a reduced glomerular filtration rate, a positive antinuclear antibody reaction, and RBC casts in the urinary sediment. Glomeruli with normal morphology (light, immunofluorescence, electron microscopy) were found on renal biopsy; however, a mild interstitial nephritis was observed that predominantly involved the distal tubules. The etiology of this inflammatory process is unknown. Changes in distal tubular function correlated with the morphology: acidification was impaired whereas concentrating ability was normal. Although RBC casts have been thought to be diagnostic of glomerular diseases, the present case demonstrates that tubulointerstitial disease can be responsible for RBC cast formation.