The impairment of superoxide anion (O2-) generation by aged polymorphonuclear cells (PMN) stimulated with formyl-methionyl-leucine-phenylalanine (FMLP) has been reported. In this work the effect of lipopolysaccharide (LPS), granulocyte-macrophage colony stimulating factor (GM-CSF) and pentoxifylline (POF) pretreatment on FMLP-triggered neutrophil oxidative metabolism in a group of healthy elderly individuals, was investigated. Results provide evidence that LPS and/or GM-CSF priming was able to enhance O2- production in old PMN, even if values were still lower than those observed in similarly-treated young cells. Moreover, even if the lag period was unaffected by inflammatory mediator treatment, the priming gave rise to a significant increase of maximum O2- release rate. On the contrary, POF pretreatment led to a significant decrease of oxidative responsiveness in either unprimed or primed PMN suspensions. These findings suggest the occurrence of different mechanisms in the imbalance of FMLP-activated neutrophil oxidative responsiveness during senescence. This may be of paramount significance for explaining the augmented frequency of severe infectious diseases with advancing age.