Inasmuch as adenine nucleotides may be secreted by platelets during inflammation, we sought to determine whether ATP and related compounds could serve as stimuli of neutrophil (polymorphonuclear cells, PMN) activation as manifested by an increase in their adhesive properties. Exposure of isolated human PMN to ATP or its nonhydrolyzable analog, adenosine 5'-O-(3-thiotriphosphate) did indeed stimulate an increase in cellular adhesive function as assessed by an increase in the surface expression of the leukocyte adhesion-promoting glycoprotein, Mo1 (CD11b/CD18), the initiation of PMN aggregation, and (in the case of ATP) the attachment of increased numbers of albumin-coated polystyrene latex beads. However, this increase in PMN adhesive function was not accompanied by the generation of products of the respiratory burst. These in vitro data suggest the possible influence of secreted adenine nucleotides in promoting neutrophil adhesion-dependent interactions at inflammatory sites in vivo.