This study describes patterns of progression of albuminuria and renal function in a subgroup of 40 patients from a total cohort of 211 diabetic patients (118 type I, 93 type II) followed over a period of 8-14 years. Forty patients (18 with type I diabetes, 22 with type II diabetes) showed progressive increases in albumin excretion rate (AER) and/or decreases in creatinine clearance (CC) during the study period. Of these, AER alone increased in 15 patients, AER increased and CC decreased in 13 patients, and CC alone decreased in 12 patients, with a similar distribution of type I and type II diabetic patients in each group. Of the 28 patients who showed an increase in albuminuria, AER increased at an annual rate of 30-40%, resulting in a 4- to 8-fold increase in AER to >20 μg/min during the study. Of the 25 patients who showed a decrease in renal function, CC decreased at an annual rate of 4-5 ml/min, resulting in an approximate halving of CC to <90 ml/min during the study. The rate of fall in CC was not related to the presence or absence of concomitant increases in albuminuria. However, a significant preponderance of women in the group showed a decline in CC alone. The decline in CC was associated with an increase in plasma creatinine as well as a progressive decrease in urinary creatinine excretion, but the underlying mechanisms remain unexplained. These data support the concept that a subgroup of diabetic patients may show a decline in renal function in the absence of significant increases in AER. Additional functional and structural data will be needed to determine if these patients have diabetic nephropathy. However, this study does suggest that albuminuria alone may not predict renal functional changes in all diabetic patients.