Prostaglandins (PGs) are believed to be involved in some of the manifestations of the acute phase response, which may be triggered by bacterial lipopolysaccharide (LPS). Glucocorticoids are part of this response and, among other things, regulate PG synthesis and are anti-inflammatory. We investigated the role of endogenous and exogenous glucocorticoids in the regulation of aortic prostacyclin synthesis and in its response to LPS. Rats were injected with LPS and their aorta incubated ex vivo. Aortic prostacyclin (PGI2) production declined 1 h after LPS injection and remained low for at least 96 h. On the other hand, LPS stimulated PGI2 production in adrenalectomized rats, although the latter had reduced capacity to synthesize PGI2, compared with sham-operated rats. Dexamethasone substitution restored synthesis. In intact rats only acute (2 h), but not repeated administration of dexamethasone, increased PGI2 production. In vitro IL-1 alpha stimulated aortic PGI2 synthesis. It is concluded that glucocorticoids may exert a biphasic influence on aortic PGI2 production, possibly through a dual action of lipocortins. Moreover, it is suggested that lipocortin requires activation before it can exert its full effect, and that agonists such as LPS may provide the stimulus for such activation.