The factors associated with intermittent microalbuminuria were studied over 7 years in 49 Type I and 53 Type II diabetics who had normal initial albumin clearance. Fasting plasma glucose, HbA1, 24 hour urinary glucose, blood pressure, protein intake (24 hour urinary urea), and the renal clearance of albumin, transferrin, and IgG, as well as total proteinuria, were assessed every 3-6 months. Fifteen Type I and 11 Type II diabetics had 40 and 31 episodes, respectively, of intermittent microalbuminuria, defined as an albumin clearance >11 nl/sec, without progressing to persistent microalbuminuria. Rises in transferrin and IgG clearance paralleled albumin clearance in both Type I and Type II diabetics. There were no significant changes in blood pressure or glycemic control during episodes of intermittent microalbuminuria. However, in Type I diabetics, intermittent microalbuminuria was associated with higher levels of urinary urea excretion. This study raises the possibility that increased protein intake may participate in the development of nephropathy in Type I diabetes.