The effects of massive doses of steroids on septic shock were tested in 48 patients being treated for extensive cellulitis, wet gangrene, or severe peritonitis. From diagnosis until maximum weight gain (average, 47 hours), they received an average of 17.7 L of crystalloid solution and 1.0 L of blood and voided 3.1 L of urine. Of the 48 patients, 23 were selected in random fashion to receive dexamethasone sodium phosphate (6 mg/kg) over 48 hours. The average age (55 years), duration of shock (36 minutes), and insult were similar for both groups. Each group received similar volumes of fluid and blood. Steroid therapy was associated with a statistically significant rise in diastolic pressure (88 v 78 mm Hg), mean arterial pressure (105 v 95 mm Hg), and central venous pressure (16 v 10 cm H2O). Concomitant blood volume was lower in patients treated with steroids (5.2 v 6.1 L). All differences between the two groups disappeared after 48 hours when steroid therapy was discontinued. No differences were noted in morbidity and five patients in each group died.