Forty-eight patients with IgA nephritis entered a 3 year controlled prospective trial using a combination regimen of cyclophosphamide for 6 months and dipyridamole and low dose warfarin for 36 months. Those in the treatment group (n = 27) had stable renal function and a significant decrease in proteinuria (p less than 0.01) but in the controlled group (n = 21) there was a significant fall in creatinine clearance (p less than 0.01) and rise in serum creatinine (p less than 0.02) with no change in proteinuria. The data suggested that the above treatment resulted in a significant reduction of proteinuria and more stable renal function. Eleven patients in the treatment group and 10 patients in the controlled group had repeat renal biopsies after the trial. Eight parameters were used in the evaluation of the renal biopsies: mesangial hypercellularity, crescents, tuft adhesion, segmental sclerosis, global sclerosis, tubular atrophy, interstitial fibrosis and vascular sclerosis. Each lesion was graded from 0 to 3 and a total scoring system used for evaluation of histological severity. In the treatment group there was no significant histological deterioration but in the controlled group there was progressive histological deterioration. Mean total histological score was 3.7 +/- 2.6 before the trial and 6.5 +/- 3.1 after the trial (p less than 0.05). This histological progression appeared to run parallel with the clinical course.