Mouse cerebral arterioles studiedin vivodemonstrated endothelium dependent responses to adenosines-diphosphate (ADP),αβmethylene adenosine triphosphate (αβMATP), 2 methyl thio adenosine triphosphate (2MeSATP), and endothelium independent dilation to 2 chloroadenosine (2-CA). Endothelium dependence was directly established by markedly inhibiting the response with focal endothelial injury produced by a light/dye technique. Based on the effects of cyclooxygenase inhibitors and N guanidino-L-monomethyl arginine on the responses it appears that the response to ADP and 2MeSATP are mediated by both a prostanoid liberated from the endothelium and by classical endothelium derived relaxing factor (EDRF) whileαβMATP is mediated by EDRF alone. Based on the effects of 8 phenyl theophylline (8 PT) on the responses it appears that a type A receptor in the vascular smooth muscle is responsible for the endothelium independent dilation produced by 2-CA. The 8 PT failed to influence the response to ADP orαβMATP. The lowest doses ofαβMATP and 2MeSATP produced endothelium independent constrictions. 8 PT inhibited the dilations produced by 2 MeSATP, a result which we could not explain.