U-74006F, a 21-aminosteroid, is a potent inhibitor of CNS tissue LP in vitro. In this study it was tested for effects on brain edema and metabolites after impact injury to the closed skull. Anesthetized cats were blindly treated with U-74006F or vehicle at 30 min (1 mg/kg) and 2.5 hr (0.5 mg/kg) after head or sham injury. They were sacrificed 4 hr after injury by in situ fixation of the brain. Head-injured cats were selected for unilateral (left) cerebral contusion. Metabolites (enzyme fluorometry) and edema (specific gravity) were measured in the cerebral cortex and white matter bilaterally. Cerebral hemisphere, contusion, and vasogenic edema volumes were morphometrically measured. Magnitude of edema and metabolites in tissue with vasogenic edema was similar in vehicle- and drug-treated cats. By contrast, the cortex and nonedematous white matter neighboring contusion in drug-treated cats had lactate, glucose, and glycogen levels that suggested an improved metabolic state over vehicle treatment. Most metabolites were not affected by trauma or treatment in the uncontused hemisphere. These results suggest that postinjury treatment with the nonglucocorticoid steroid U-74006F may benefit the metabolism of nonedematous tissue adjacent to contusion.