The effects of adenosine and some related purines on the K+-induced release of 3H-noradrenaline from rat cerebral cortex slices were determined in a superfusion system. Adenosine and ATP caused a dose-dependent inhibition of 3H-NA release with a maximal effect of 35% at 10(-4) M. Theophylline, 10(-4) M, antagonized the inhibitory effect of adenosine. The results support the hypothesis that at least some of the central stimulant effects of the methylxanthines could be related to blockade of a purinergic inhibitory tone on noradrenergic synaptic output.