Acute uremia was induced in male Swiss albino mice by complete urethral ligation and the animals were sacrificed 2, 4-6, 24, and 48 h after operation. Sham-opeated animals (without the urethral ligation) were similarly treated. The blood urea levels of animals with total urinary tract obstruction went up to 175 mg/100 ml at 4-6 h of urethral ligation and reached an average level of 827 mg/100 ml at 48 h, while the control group exhibited and average blood urea level of 37 mg/100 ml. Lysosomes obtained from livers of uremic mice sacrificed at different time intervals demonstrated a lability of the lysosomal membranes (as determined by the acid phosphatase activity in mU/mg) which was maximal at 4-6 h of urethral ligation, declining towards normal at 24 and 48 h, despite an increase in the animal's blood urea. In vitro studies exposing liver lysosomes to progressively higher urea concentrations (differences of as much as 100,000 times) did not reveal any effect of urea upon the stability of lysosomal membranes. The reason for the lability of lysosomal membranes in the uremic group was not apparent in the present study.