As measured by extracellular single-cell recording, the responses to adenosine triphosphate (ATP) by ATP-sensitive chemoreceptors (ATP cells) on the olfactory organ of the spiny lobster are markedly suppressed by adenosine diphosphate (ADP), adenosine monophosphate (AMP) and to a lesser extent, adenosine, when each is presented in binary mixture with ATP. In the presence of ADP, the dose-response function for ATP exhibits an apparent parallel displacement to the right suggesting that this antagonism may occur via competition at the ATP receptor. Structure-activity relationships reveal that the structural requirements for antagonism by diphosphate analogs of ADP bear little relationship to the requirements for the agonistic activity of corresponding triphosphate analogs. Under Mg2+-free conditions, the desensitization of ATP cells tends to be delayed resulting in enhanced responses to ATP. Desensitization does not appear to be related to the generation of the antagonist, ADP, from ATP via ecto-ATPase activity. The results of this study suggest that the responses of ATP cells to the ATP contained in natural stimulus (odor) mixtures can be tempered by the suppressive interactions of other nucleotides in the mixtures. Furthermore, these interactions may be mitigated and/or intensified by the actions of sensillar ectonucleotidases.