Luminol-enhanced chemiluminescence (LECL) was used to determine the effect of soluble CD14 (sCD14) on the endotoxin inducible generation of reactive oxygen species in human monocytes. LPS is unable to activate monocytes under serum free conditions, but LECL responses were measured after pretreatment of LPS stock solution with serum, according to Wright et al., who described a LPS-binding protein (LBP), necessary for mediating LPS binding to the receptor CD14 on monocyte surfaces. In normal human serum a soluble form of CD14 (sCD14) exists, from which nothing is known about its possible function. sCD14 reduces the endotoxin inducible monocyte activation in our in vitro model in a dose dependent manner (5-30 micrograms/ml) suggesting an immunomodulatory function. Therefore it seems to be a new candidate for a therapeutic concept in endotoxic shock prevention.