HL‐60 cells are human promyelocytic cells expressing two ATP receptors: the P2Y₂ and P2Y₁₁ subtypes. Our Northern blotting experiments have shown that P2Y₂ and P2Y₁₁ messengers were up‐regulated in these cells, rapidly and independently of protein synthesis, following treatment with granulocytic differentiating agents such as retinoic acid, dimethylsulfoxide, granulocyte‐colony stimulating factor, dibutyryl cyclic AMP and ATP. AR‐C67085 and adenosine 5′‐O‐(3‐thiotriphosphate), two potent agonists of the recombinant P2Y₁₁ receptor, increased intracellular cAMP concentration in HL‐60 cells more potently than ATP itself. These observations support the conclusion that the effect of ATP on HL‐60 cell differentiation is mediated by the P2Y₁₁ receptor.