Relationship of systemic blood pressure to nephropathology in insulinédependent diabetes mellitus. Although hypertension is an important complication of diabetes it is unclear whether its association with other diabetic complications represents cause or consequence. Our study is a cross sectional evaluation of the relationship of blood pressure to renal structural and functional parameters. In 139 patients with insulin dependent diabetes for 18.9 ± 7.4 years (mean ± SD), we divided the patients into those with markedly increased mesangial volume fraction [Vv(mes/glom) ≥ 0.37] and those with less [Vv(mes/glom) < 0.37]. Hypertension (systolic BP ≥ 160 and/or diastolic BP > 90 mm Hg or receiving BP medications) occurred in 29/40 with Vv(mes/glom) ≥ 0.37. All 40 had clinical nephropathy with urinary albumin excretion (U_AE) > 200 mg/24 hr. By two-way ANOVA creatinine clearance was lower and albuminuria was increased with both hypertension and the expanded mesangium. Also other measures of renal structure including filtration surface, index of interstitial fibrosis and index of arteriolar hyalinosis were increased by hypertension and mesangial expansion. Most patients with hypertension had other criteria for clinical nephropathy. Since, in these studies, we could not determine if hypertension contributed to or resulted from the renal lesions, we developed an estimate of the rate of mesangial expansion. We found that patients with normal BP (119 ± 11/78 ± 7 mm Hg) can be rapidly developing mesangial expansion. These studies support the view that the development of serious renal lesions can be independent of hypertension in 1DDM. Further elucidation of the role of blood pressure in the genesis of diabetic glomerulopathy will require longitudinal studies of both renal structure and function in the first decade of IDDM.