Persistent microalbuminuria [albumin excretion rate (AER): 30-300 micrograms/min] is predictive of clinical nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) and cardiovascular mortality in addition to nephropathy in patients with non-insulin-dependent diabetes. The clinical significance of intermittent microalbuminuria, however, is unknown. We performed serial measurements of urinary albumin excretion at intervals of approximately 6 months in 139 diabetic patients who at entry did not have persistent microalbuminuria to determine whether intermittent microalbuminuria occurs more frequently in those patients who subsequently develop persistent microalbuminuria. The relative risk for the development of persistent microalbuminuria in diabetic patients with a greater proportion than 3 out of 20 determinations in the microalbuminuric range was 17.4 (95% confidence interval, 3.92-77.2) in those with IDDM and 2.78 (0.99-7.8) in those with non-insulin-dependent diabetes when compared with matched diabetic patients with fewer elevated measurements. These data suggest that frequent intermittent microalbuminuria predicts the future development of persistent microalbuminuria particularly in IDDM patients and that AER should be assessed by serial rather than single measurements.