Urinary excretion of various renal prostaglandins was measured by radioimmunoassay and gas chromatography-mass spectrometry in children who had different degrees of metabolic control. Excretion in PGE2 in diabetic children was twice control values irrespective of the presence or absence of diabetic ketoacidosis (DKA). The urinary excretion of PGF2 alpha was significantly increased in diabetic children with ketoacidosis, but not when diabetes was well controlled. The excretion of 13, 14 dihydro-15-keto PGE2, the major metabolite of circulating PGE2, was increased in all diabetic children, and was most elevated in ketoacidosis when it averaged 10 times basal excretion. Urinary excretion of PGF2 alpha and of 6-keto-PGF1 alpha, the metabolite of PGI2, was approximately doubled in DKA compared with values from healthy subjects. Excretion of PGE2 was twice control values in children with stable diabetes, whereas the equivalent value for TXB2, the metabolite of the active vasoconstrictor TXA2, was reduced by approximately 50%. We suggest that the increased excretion of prostacyclin metabolite may result from a protective biological action on the kidney opposing other vasoconstrictor hormone activity. PGE2 appears not to be involved in this process. The highly elevated excretion of PGE2 metabolite may represent an activation of systemic PGE metabolism during DKA.