The effect of streptozotocin-induced diabetes mellitus on prostacyclin (PGI2) production by the urinary bladder in rats was investigated. Acute ketotic (two days duration) and non-ketonuric (seven days duration) diabetes had no effect on PGI2 production by the aorta or the bladder. "Chronic" untreated non-ketonuric (62 days duration) diabetes had a marked inhibitory effect on aortic PGI2 secretion which was not observed when rats were treated with insulin. Urinary bladders from animals with "chronic" untreated non-ketonuric diabetes were larger and heavier, and their walls were hypertrophic. The bladders from these latter animals produced more total PGI2, as well as more PGI2 per unit weight. Enhanced PGI2 production by bladders from animals with untreated non-ketonuric diabetes indicates that: 1) severity of the metabolic disturbance due to diabetes mellitus (ketosis) is not as important as the duration of diabetes as far as the induction of changes in PGI2 production is concerned; 2) distension and hypertrophy of the bladder and hyperosmolar urine are probably more potent stimulators of PGI2 production than diabetes is an inhibitor; 3) diabetes mellitus may have a variable effect on PGI2 secretion patterns in different tissues; 4) urinary excretion of PGI2 or its stable metabolite, 6-oxo-PGF1 alpha may not exclusively reflect PGI2 production by systemic vasculature and/or the kidneys; and 5) good control of diabetes prevents the bladder wall and PGI2 synthesis changes.