Sodium butyrate, which directly affects chromatin structure and function in many cells, is as effective as granulocyte-macrophage colony-stimulating factor (GM-CSF) in delaying apoptosis in human neutrophils. Both butyrate and GM-CSF preserved the ability of neutrophils cultured for 22 h in vitro to generate reactive oxidants and express receptors such as CD16. They also delayed apoptotic morphology and DNA fragmentation, and stimulated de novo biosynthesis: newly-labelled polypeptides detected by 2D-polyacrylamide gel electrophoresis after treatment with GM-CSF and butyrate were very similar. Cycloheximide abrogated the effects of both GM-CSF and butyrate. Exposure to butyrate for 1 h did not prime oxidant production and did not up-regulate expression of CD11b. Hence, unlike GM-CSF, butyrate does not stimulate translocation of granules to the plasma membrane. These data suggest that active gene expression is involved in the regulation of neutrophil apoptosis and changes in chromatin structure and function may control apopotosis in these cells.