In order to improve our possibility of establishing a long-term prognosis in IgA nephritis, 73 patients out of a cohort of 282, followed over a mean period of 12 years at the same institution for an IgA nephritis, had a prospective second renal biopsy 5 years later. For all biopsies (RB1 and RB2), we developed a quantitative scoring for all elementary lesions with a glomerular, an interstitial, a tubular and a vascular index. The sum of these 4 indexes gave a global optical score (GOS). Pathological improvement on light microscopy (delta GOS less than or equal to -2) was noticed only in 3 patients (4%), stability (-2 less than delta GOS less than +2) in 30 patients (41%), mild deterioration (+2 less than or equal to GOS less than 5) in 23 patients (32%) and major progression (delta GOS greater than or equal to 5) in 17 patients (23%). We observed no pathological remission, even in the 14 patients with complete clinical remission. The pathological progression was characterized by an increase in all elementary lesions, mainly the tubulo-interstitial and vascular ones. By immunofluorescence mesangial IgA deposits remained stable with no disappearance; however, the number and intensity of vascular C3 deposits were significantly greater on RB2. Chronic renal failure (serum creatinine greater than 1.5 mg/dl) correlated best with major pathological progression and mainly with the progression of extraglomerular lesions. IgA nephritis is a slowly progressive disease with no pathological remission, and its evolution is characterized by progression of extraglomerular lesions, mainly vascular, which might play a major role in the ultimate development of chronic renal failure.