1 5'-N-ethylcarboxamidoadenosine (NECA) is an adenosine analogue which is 22,900 times more potent than adenosine as a vasodilator. Adenosine and some of its analogues are also inhibitors of human platelet aggregation. NECA was tested for its effects on human platelets. 2 NECA (1 microM) inhibited human platelet aggregation induced by adenosine 5'-diphosphate (ADP), adrenaline, 5-hydroxytryptamine (5-HT) and thrombin more powerfully than adenosine. NECA was 5 to 10 times more potent than adenosine at inhibiting ADP- and adrenaline-induced aggregation. 3 NECA, like adenosine, caused dose-dependent increases in levels of platelet adenosine 3',5'-cyclic monophosphate (cyclic AMP), which were competitively inhibited by theophylline, an adenosine antagonist. 4 These effects of NECA, like those of adenosine, were completely stereospecific as the L-enantiomer of NECA was inactive. 5 NECA did not interfere with the inhibition by ADP of prostaglandin E1 (PGE1)-stimulated adenylate cyclase. 6 NECA is the most potent analogue of adenosine tested so far on human platelets, and is the first example of a 5' modification to retain affinity for the platelet adenosine receptor.