Tubulointerstitial renal disease is found frequently in patients with systemic lupus erythematosus. Despite the frequency of this entity, little is known about the prognostic significance of this biopsy finding. We reviewed 46 consecutive renal biopsy specimens from patients with systemic lupus erythematosus who were followed up for a mean of 5.4 years. Tubulointerstitial abnormalities were present in 39% of the entire group of patients and in 51% of the patients who had clinical evidence of renal abnormalities. Tubulointerstitial inflammation was closely associated with diffuse proliferative glomerulonephritis, with elevation of serum creatinine (SCr) concentration at biopsy, and with increased frequency of proteinuria both at biopsy and at follow-up. Additionally, active interstitial inflammation was associated with an increased risk of doubling the entry SCr concentration. The presence or absence of tubulointerstitial disease, however, did not add additional prognostic information to the predictive power of the entry SCr concentration or the glomerular histologic features.