21-Aminosteroids have been shown to attenuate neuronal damage and to improve neurological outcome after experimental ischemia. The aim of this study was to determine whether brain edema induced by a cryogenic injury can be influenced by the 21-aminosteroid U-74389F. A cortical freezing lesion was applied to the right parietal region of Sprague-Dawley rats under ketamine-xylazine anesthesia. Systemic blood pressure was monitored in the peritraumatic period. Four different doses of U-74389F (A-D) were studied for their effect on post-traumatic brain swelling and edema. Respective control groups received only the solvent, citric acid buffer. (A) 3 mg/kg b.w.i.p. (total dose) 30 min before, 1 and 12 h; post trauma (p.t.); (B) 9 mg/kg b.w.i.v. 30 min before, 1 and 12 h p.t.; (C) 25 mg/kg b.w.i.v. 30 min before, 1, 6, and 12 h p.t.; (D) 50 mg/kg b.w.i.v. 15 min before, 15 and 30 min as well as 1, 2, 6, and 12 h p.t. 24 h after trauma, brains were removed and hemispheric swelling and water content were determined from the difference between wet and dry weight. Application of the 21-aminosteroid U-74389F moderately reduced post-traumatic brain swelling in all treatment groups: (A) 5%, (B) 9%, (C) 12%, and (D) 14%. In parallel with this, the increase in water content of the traumatized hemisphere was marginally lowered by U-74389F in all groups; in (C) e.g. from 1.9 +/- 0.1% to 1.7 +/- 0.1%, p = 0.07. These two findings taken together indicate that the 21-aminosteroid U-74389F moderately reduces post-traumatic swelling and edema.