The release of the inhibitory amino acid taurine is markedly enhanced under ischemic conditions in both adult and developing brain stem, together with a pronounced increase in the release of the neuromodulator adenosine. We now studied the effects of adenosine receptor agonists and antagonists on [3H]taurine release in the brain stem in normoxia and ischemia, using a superfusion system. Under standard conditions, the adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA) potentiated basal taurine release in adult mice, which response was blocked by the antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). CHA and the A2a receptor agonist 2-p-(2-carboxyethyl)phenylamino-5′-N-ethylcarboxaminoadenosinehydrochloride (CGS 21680) had no effect on the release in developing mice. In ischemia, CHA depressed both basal and K+-stimulated taurine release in developing mice in a receptor-mediated manner, blocked by DPCPX. The A2a receptor agonist CGS 21680 was also inhibitory. Taurine and adenosine may thus not cooperate in developing mice to prevent ischemic neuronal damage. On the other hand, CGS 21680 enhanced taurine release in the adult brain stem in ischemia, both basal and K+-stimulated release being affected. These effects were abolished by the antagonist 3,7-dimethyl-1-propargylxanthine (DMPX), indicating a receptor-mediated process. In this case elevated levels of taurine could be beneficial, protecting against hyperexcitation and excitotoxicity.