We tested a wide range of pro-inflammatory cytokines for their capacity to activate protein synthesis in neutrophils as analyzed b y [35S] methionine metabolic labelling experiments. Of all the cytokines tested, only GM-CSF and TNF alpha stimulated significant synthesis and secretion of a 23 kD protein which resolved into two bands on two dimensional gels. Under non-reducing conditions on one dimensional gels, its migration pattern remained the same indicating that the two bands most likely represent isoforms of the same protein. Immunoisolation studies using antibodies directed against size-relevant molecules did not lead to the identification of this molecule. The fact that this 23 kD molecule is induced in a highly specific and selective manner by GM-CSF and TNF alpha indicates that it may play a key role in some of the responses of neutrophils to these two cytokines. Therefore, full characterization of this 23 kD protein could provide important new knowledge on the mechanisms by which these two cytokines exert their biological effects on neutrophils.