Effects of the new chemical agent, bifemelane, on ischemic cerebral edema were studied in 70 mongolian gerbils. Five different doses of bifemelane (0.2-25.0 mg/kg) as well as saline were administered intraperitoneally in 6 groups of animals (n = 46), and 30 min afterward both common carotid arteries were occluded. The brain was removed 90 min after the occlusion, and the cerebral water content (CWC) in the bifemelane treated groups and the controls was compared. To assess hemodynamic effects of bifemelane, regional cerebral blood flow (rCBF) was also measured in 24 animals using hydrogen clearance techniques. The CWC in the saline-treated controls (79.9 +/- 0.4%) was significantly increased compared to the normal values (78.4 +/- 0.3%). The CWC in the groups receiving 1 mg/kg, 5 mg/kg and 10 mg/kg of bifemelane showed 79.3 +/- 0.3%, 79.5 +/- 0.2% and 78.9 +/- 0.3%, which were significantly lower than the controls (p less than 0.005, p less than 0.02, p less than 0.001). Thus, bifemelane reduced a development of ischemic cerebral edema in a dose-dependent manner. The rCBF in the bifemelane groups and the controls measured before the drug administration was the same ranging within 35.0-37.0 ml/100 g brain/min. The administration of bifemelane produced small rCBF increase. After the carotid artery occlusion, rCBF in all control animals decreased below 6.0 ml/100 g brain/min, the critical level for cellular ion-pump function. The majority of bifemelane-treated animals also showed a similar flow reduction. However, in 33% of animals receiving 10 mg/kg or 25 mg/kg of bifemelane, rCBF was maintained above this critical level.(ABSTRACT TRUNCATED AT 250 WORDS)