Submerged rat hippocampal slices were exposed to hypoxic medium prepared with 95% N2/5% CO2. The population spikes recorded from CA1 cell layer were completely blocked within a range of 5-10 min. The adenosine antagonist theophylline (100 microM) delayed and partially prevented the hypoxia-induced depression. Increasing concentrations of the more potent adenosine antagonist 8-phenyltheophylline (8-PT; 0.1, 1, 10 microM) resulted in progressively less hypoxia-induced depression. The antidromically elicited afterpotentials recorded in the absence of synaptic transmission in low calcium, high magnesium medium were blocked within 8 min of hypoxia. Theophylline (100 microM) and 8-PT (10 microM) delayed to a similar extent the hypoxia-induced depression of the first afterpotential but did not prevent its complete depression.