The effect of the xanthine derivatives theophylline and ropentofylline (HWA 285) on postischemic selective nerve cell damage was studied in the hippocampus of the Mongolian gerbil and assessed by measuring the decrase of Nissl staining in the CA1 area. Theophylline administered 15 min prior to a 2-min period of bilateral carotid occlusion led within 4 days to a marked damage of CAI neurons which was not seen in untreated animals. Prolonged of the ischemic period to 5 min led to the same degree of damage in theophylline-treated and untreated animals revealing that the protective power of endogenous adenosine is limited. In contrast to theophylline, treatment with propentofylline (10 mg/kg i.p.) antagonized cell death: such a protection by propentofylline was also achieved after 5 min ischemia in animals treated with theophylline. This indicates that propentofylline does not exert its protective effect via adenosine-mediated mechanisms.