Polymorphonuclear leukocytes (PMNL) are prominent at sites of acute inflammation. Their infiltration is stimulated under pathological conditions by a variety of agents which include bacteria, immune complexes and complement derived chemotactic peptides. Recently attention was focussed on the 5-lipoxygenase product leukotriene B4 (LTB4) which has been demonstrated to induce the key features associated with an acute inflammatory reaction. However, evidence supporting a pro-inflammatory role for LTB4, and therefore the anti-inflammatory efficacy of 5-lipoxygenase inhibitors, is largely circumstantial. Moreover, there are concerns that other chemotactic factors, notably C5a, may compensate for the absence of LTB4. Here we challenge this view and, on the basis of recent experimental and clinical data suggest that LTB4 does not simply duplicate the activity of C5a. Instead we propose that their predominant site(s) of action differ in such a way that they may synergise in mediating PMNL recruitment.