The effects of extracellular divalent cations on the responses of human platelets to adenosine 5'-diphosphate (ADP) and on its inhibition by the competitive antagonist adenosine 5'-triphosphate (ATP) were investigated. Two responses were studied, shape change and the inhibition of prostaglandin E1 (PGE1)-stimulated adenylate cyclase, and experiments were carried out in the presence of divalent cations (Ca2+ and Mg2+, 1 mM) or in their absence. For each response there was a small leftward shift of the concentration-response curve to ADP in the absence of divalent cations compared to that in their presence, and this leftward shift disappeared when the results were plotted in terms of ADP3- rather than total ADP concentration. The shape change results were, however, complicated by a reduction in the maximal response to ADP in the absence of divalent cations. For each response there was also a marked increase in the pA2 value of ATP in the absence of divalent cations compared to that in their presence, and this difference disappeared if the results were calculated in terms of ATP4- instead of total ATP. These results suggest that the human platelet ADP receptor, in common with other receptors for adenine nucleotides, recognises predominantly the uncomplexed forms of ADP and ATP as ligands.