Background. In type 2 diabetic patients without retinopathy the cause of albuminuria is heterogeneous and our knowledge of the relationship between kidney structure and function in these patients is limited. Therefore, a long-term study evaluating the structural-functional relationship in albuminuric type 2 diabetic patients without retinopathy was performed. Methods. Mesangial volume of total glomerular volume (Vv (mes/glom)), fractional area of focal interstitial fibrosis and tubular atrophy of cortical area (FF) and percentage of sclerosed glomeruli (S/G) were measured on kidney biopsies from 49 type 2 diabetic patients without retinopathy. Glomerular filtration rate (GFR) was determined at least 3 times (median 8 (range 3-20)) in each patient. Patients were followed for 7.0 (1.1-17) years. Albuminuria and blood pressure were measured every 3-6 months. Results. Biopsies revealed diabetic glomerulopathy (DG-group) in 69%) of the patients (27 male/7 female) and normal glomerular structure (n = 9) or glomerulonephritis (n = 6) were found in 31% (13 male/2 female) (NDG-group). In the DG-group GFR decreased from 97 +/- 5 to 66 +/- 5 ml/min/1.73 m(2) (mean SE) (P < 0.001), with a rate of decline in GFR of 5.3 +/- 0.8 ml/min/year and in the NDG-group from 93 +/- 7 to 74 +/- 11 ml/min/1.73 m(2) (P < 0.01), with a rate of decline in GFR of 3.2 +/- 0.9 ml/min/year, P = 0.09 between groups. Mean arterial blood pressure decreased from 109 +/- 2 to 100 +/- 2 mm Hg (P < 0.001) (DG-group) and remained unchanged in the NDG-group. An association between Vv (mes/glom) and rate of decline in GFR was revealed mainly in the NDG-group (DG-group: r = 0.31, P = 0.07 and NDG-group; r = 0.74, P < 0.01). Furthermore, the rate of decline in GFR seemed to be associated with FF in the NDG group (r = 0.48, P = 0.07). Percentage of S/G was not associated with the rate of decline in GFR. Vv (mes/glom) was associated with mean albuminuria during follow-up in the DG group; r = 0.38. P < 0.03 (NDG group; r = 0.51, P = 0.09). Albuminuria was an independent predictor of the rate of decline in GFR in both groups (DG-group, r = 0.40, P < 0.05 and NDG-group; r = 0.61, P < 0.01). Conclusions. Our study revealed a tendency to a faster rate of decline in GFR in the DG-group compared to the much smaller NDG-group, characterized by marked heterogeneity of the underlying kidney lesions and rate of GFR loss. A large mesangial volume fraction was associated with increased albuminuria and loss in GFR. Albuminuria acted as a progression promoter in both groups.