We analyzed brain tissue in 139 rats for adenosine and its metabolites, inosine and hypoxanthine, during the initial 120 seconds of seizures induced by bicuculline. We also measured ATP, ADP, AMP, phosphocreatine (PCr), and lactate. We divided the rats into four groups by adjustment of their preictal arterial oxygen tension: group I, PaO2> 200 mm Hg), adenosine increased within ten seconds of the onset seizures and remained elevated even after 120 seconds. Elevations in inosine and hypoxanthine were delayed compared to the increases in adenosine. A reduction PaO2(50 mm Hg) or systemic blood pressure during seizures caused a further augmentation in the increase brain adenosine levels. During the seizure period, transient changes in adenine nucleotides and energy charge were observed, but PCr remained de-pressed and lactate continued to rise. The rapid sustained increase in cerebral adenosine levels, temporally paralleling the changes in cerebral blood flow, supports role for adenosine the regulation of cerebral blood flow.CircRes 47: 568-577, 1980