Proteinuria and nephropathy have been found to cluster in families of non-insulin-dependent diabetic (NIDDM) Pima Indian, and in Caucasian insulin-dependent diabetic (IDDM) patients. No information is at present available for Caucasian NIDDM patients. The aim of the present study was to determine whether micro-macroalbuminuria (AER+) is associated with albumin excretion rate abnormalities in diabetic and non-diabetic siblings of probands with NIDDM and AER+. We identified 169 Caucasian families with one NIDDM proband (the patient with longest known NIDDM duration) (101 families with only NIDDM siblings, 33 families with both NIDDM and non-NIDDM siblings and 35 families with only non-NIDDM siblings). Of the probands 56 had AER+ [Prob-NIDDM-(AER+)], 78 had AER-[Prob-NIDDM-(AER-)], 74 siblings of Prob-NIDDM-(AER+), and 113 siblings of Prob-NIDDM-(AER-) also had NIDDM. Data on albuminuria and retinopathy from multiple sibling pairs when the size of the sibship was more than two was adjusted according to a weighting factor. The odds ratio for AER+, in siblings of Prob-NIDDM-(AER+) adjusted for age, hypertension, glycated haemoglobin A1c and other confounding variables was 3.94 (95% confidence intervals: 1.93-9.01) as compared to siblings of Prob-NIDDM-(AER-). The 74 siblings of Prob-NIDDM-(AER+) had higher prevalence of proliferative retinopathy than siblings of Prob-NIDDM-(AER-) (14 vs 2%; p < 0.01). We also identified 66 non-diabetic siblings of 41 NIDDM probands with AER+ and 36 non-diabetic siblings of 27 NIDDM probands with AER-. Albumin excretion was two times higher, although still within the normal range, in the non-diabetic siblings of Prob-NIDDM-(AER+) than in siblings of Prob-NIDDM-(AER-) [median = 13.5 (range 0.5-148) vs 6.6 (range 1-17) micrograms/min (p < 0.05)]. In conclusion higher rates of albumin excretion aggregate in Caucasian families with NIDDM. Proliferative retinopathy is more frequently observed in families showing a clustering of AER+ and NIDDM. These findings suggest that familial factors play a role in the pathogenesis of renal and retinal complications in NIDDM.