Current knowledge regarding the concordance and discordance of the eye and kidney complications of diabetes is based on observations by ophthalmoscopy of retinal structural changes, which may be present at early stages of the disorder, and renal functional changes, which only become apparent at the later stages of the disease. For this reason we investigated the relationship between retinal structural lesions and quantitative measures of glomerular structure in patients with insulin-dependent diabetes mellitus (IDDM). Renal biopsies were evaluated using morphometric techniques, and retinopathy classification was determined by retinal fundus photography in 86 patients with IDDM: age 30.4 +/- 7.3 years and duration of IDDM 18.9 +/- 6.3 years (mean +/- SD). Retinopathy score correlated with glomerular basement membrane width (r = 0.39, P = 0.0002), mesangial volume fraction (VvMes/Glom) (r = 0.35, P = 0.0009), surface density of the peripheral capillary wall (SvPGBM/Glom) (r = 0.34, P = 0.0013), and index of arteriolar hyalinosis (r = 0.36, P = 0.0008). Abnormalities in VvMes/Glom and SvPGBM/Glom were more pronounced in patients with both retinopathy and hypertension. Four of the 15 patients (27%) with either normal urinary albumin excretion (UAE) or low-level microalbuminuria had advanced retinopathy but normal VvMes/Glom. In conclusion, the presence of advanced retinal disease with or without hypertension in patients with IDDM indicates a greater likelihood of advanced nephropathy as evidenced by increased VvMes/Glom and decreased SvPGBM/Glom. However, marked discordance between retinopathy and nephropathy occurs, as illustrated by patients with normal UAE or low-level microalbuminuria, normal glomerular structural measures, and advanced retinopathy.