Des-amino-D-arginine vasopressin (DDAVP) stimulates the release of factor VIII and plasminogen activator from the vascular endothelium. An infusion of exogenous factor VIII given to haemophiliacs causes an increase in platelet activation. This activation does not occur after stimulating a rise in the patient's own factor VIII level caused by DDAVP infusion. We hypothesised therefore that DDAVP could also cause the endothelial release of prostacyclin (PGI2), a potent anti-platelet agent which would counteract the aggregating effect of factor VIII. To examine this possibility we studied the effect of DDAVP on prostacyclin release, as measured by its stable metabolite 6-oxo-PGF1 alpha, in vitro and in vivo. Rabbit aortic rings were incubated with different concentrations of DDAVP using saline as control. The supernatant was assayed for 6-oxo-PGF1 alpha by radioimmunoassay. All concentrations of DDAVP gave a significant release of 6-oxo-PGF1 alpha. Vasopressin was much less potent. When DDAVP was infused into haemophilic patients there was a significant increase in circulating 6-oxo-PGF1 alpha levels immediately after the infusion. The facial flushing observed as a side-effect of DDAVP could therefore be prostacyclin-mediated. We confirmed this by abolishing the DDAVP induced flushing seen in normal subjects by prior treatment with aspirin which inhibits PGI2 formation.