The ocular response to circulating bacterial endotoxin (E coli 055:B5, 100 microgram/kg) can be either significantly reduced or made more servere by pretreatment with the synthetic glucocorticoid triamcinolone. A single injection (25 mg/kg) 3 hr prior to endotoxin sharply curtails the response. Daily injections for 3 days preceding endotoxin produces an enhanced response. With this regimen, an enhanced alteration in ocular vascular permeability is produced 4 hr following endotoxin if 5 mg of triamcinolone is injected daily; if larger quantities of steroid are employed (25 mg), there is a slight reduction in ocular vascular permeability, but an enhanced intravascular fibrin accumulation in ocular blood vessels as well as in capillaries of renal glomeruli (generalised Shwartzman reaction). Once the enhancement of the ocular response to endotoxin has been established by prior treatment with steroids, additional triamcinolone given 2--3 hr before endotoxin is no longer effective in protecting against ocular or renal changes. These divergent effects of steroid could be produced by either subcutaneous or intra-orbital injection, and the response was equal in both eyes following intra-orbital injection, suggesting that steroids probably do not exert their effects locally in this situation. Although different mechanisms of action of corticosteroids may be responsible for these diverse effects, it is suggested that a loss of responsiveness to steroids may be important in their ability to enhance the effects of endotoxinemia.