Perfusion of hippocampal slices with magnesium-free media elicits epileptiform activity attributable partly to the activity of N-methyl-D-aspartate (NMDA) receptors, but recent reports have documented an NMDA-independent enhancement of orthodromic potentials by moderate reductions in magnesium concentration. The present experiments indicate that this enhancement is comparable with that produced by perfusion with an adenosine antagonist, 8-phenyltheophylline, and that superfusion with this compound or adenosine deaminase precludes any enhancement of potential size in low magnesium solutions. The low magnesium enhancement is probably attributable to the recently described magnesium dependency of presynaptic inhibition by adenosine.