The diagnosis of recurrent renal disease after transplantation is dependent on an accurate and complete diagnosis of the initial cause of renal failure and a similar determination of the cause of graft failure. To be classified as recurrent, the disease in the renal graft must be identical to that seen in the native kidneys. Recurrence of disease accounts for less than 2% of all graft failures, but the overall incidence of recurrent disease is probably 5 to 10 times more common. The most frequent cause of recurrent disease is glomerulonephritis, which was first recognized to recur soon after renal transplantation was introduced. It was then recognized that a variety of metabolic disorders would recur, but it has taken 25 years of experience for a clear picture to emerge of recurrence in most conditions. No initial cause of renal failure poses a contraindication to at least one attempt at transplantation, although with Fabry's disease and oxalosis, a special assessment of the risks for the individual recipient is warranted. In some patients, experience has shown the need for a delay in the commitment to transplantation (eg, in those with anti-glomerular basement membrane [GBM] antibody glomerulonephritis or Henoch Schonlein purpura), the need for the choice of a particular immunosuppressive regimen (eg, in hemolytic uremic syndrome [HUS]), the need for avoidance of primary nonfunction (eg, in oxalosis), and the desirability of avoiding live kidney donation (eg, in heterozygote donors in Fabry's disease, high-risk recipients with focal glomerulosclerosis, and in recipients with HUS). Probably all types of glomerulonephritis recur, but with great variation in frequency and severity. In some forms of glomerulonephritis, recurrence may be frequent and definite on histopathological criteria but may only have a minor clinical expression (eg, dense deposit disease, anti-GBM antibody glomerulonephritis, IgA nephropathy), but in others, recurrence is less predictable yet it is clearly associated with premature graft failure (eg, focal glomerulosclerosis, membranous nephropathy). A common theme emerging is that where the initial glomerulonephritis is aggressive and causes kidney failure over a short time, recurrence is more likely, and when present, it will lead to graft failure with an increased frequency. Clinical manifestations, the frequency of recurrence, and the prognosis of the graft are now identified for most conditions. Unexpected observations have included the rarity of recurrent systemic lupus erythematosus (SLE), the immediate return of heavy proteinuria in focal glomerulosclerosis, and the predictable return of dense deposit disease.(ABSTRACT TRUNCATED AT 400 WORDS)