Glucose-free medium (aglycaemia) caused a complete failure of CA1 population spikes (after 14.5 +/- 0.8 min) and field EPSPs (after 18.1 +/- 0.5 min). In the presence of the selective adenosine A1 antagonist, 8-(p-sulfophenyl)theophylline (10 microM), population spikes and EPSPs were decreased by only 13.8 +/- 11.9% and 32.4 +/- 11.6% at the end of 17.0 +/- 3.0 min and 19.8 +/- 1.7 min of aglycaemia, respectively. A similar effect was produced by caffeine (0.2 mM). The ATP-sensitive K+ channel blockers tolbutamide (1 mM) and glibenclamide (10 microM) had no significant effect on aglycaemic suppression of synaptic transmission. These observations indicate that endogenous adenosine, but not ATP-sensitive K+ conductance, plays a major role in hypoglycaemia failure of transmission.