The metabolic turnover rate and transcapillary escape rate of albumin were studied with 131I-labelled human albumin in nine patients with long-term diabetes mellitus. Retinopathy was present in all patients and nephropathy in four. Plasma albumin concentration and plasma volume were reduced (P smaller than 0.05). The previously reported decrease in the intravascular albumin mass in long-term diabetics was thus confirmed by an average of 59.0 g/m2 surface area, compared with a normal value of 71.7 g/m2-(minus18%) (P smaller than 0.005). The albumin metabolic rate was increased, the fractional disappearance rate being an average 13.2% of the intravascular albumin mass per 24 hr, compared with a normal value of 8.4% (+ 57%) (P smaller 0.001). The rate of synthesis was 7.7 g - 24 h-1 - m-2 in contrast to a normal rate of 6.2 g - 24 h-1 - m-2 (+24%) (P smaller 0.001). Total body albumin mass was decreased proportionally to the intravascular mass. Confirming previous observations, we found an increase in the transcapillary escape rate of albumin (fraction of intravascular albumin mass passing to the extravascular space per unit time) from a normal average of 5.6% - hr-1 to 7.4% - hr-1 (+32%) (P ssmaller than 0.001). This finding can best be explained by an increased microvascular permeability to plasma proteins. A positive correlation between the transcapillary escape rate and fractional disappearance rate of albumin was demonstrated ( r equals 0.74; P smaller than 0.01). This supports the concept that albumin is catabolized in connection with its permeation through the microvascular endothelium.