Polymorphonuclear neutrophils, when stimulated, rapidly form platelet-activating factor (PAF) and metabolize their arachidonate into 5-hydroperoxyeicosatetraenoate (5-HPETE), 5-hydroxyeicosatetraenoate (5-HETE), leukotriene (LT)A4, and LTB4. PAF and LTB4 degranulate neutrophils; 5-HETE, while lacking intrinsic degranulating actions, potentiates these responses. We now find that: a) 5-HPETE similarly potentiates the two lipids and has weak degranulating actions, b) LTA4 and LTB4 degranulate neutrophils by a common pathway, c) PAF degranulates neutrophils by a distinctly different pathway, d) the actions of either LT are additive to those of PAF, e) 5-HETE is particularly effective in potentiating response to combinations of PAF and LTB4, and f) combinations of the lipids partially circumvent requirements for cytochalasin B in these degranulation responses. Thus, the five lipids can be classified into potentiators (i.e., 5-HPETE and 5-HETE) and two types of independently acting agonists (i.e., LT's are one type, PAF a second type). At low concentrations, potentiator, LT, and PAF can all interact to produce prominent responses. They may similarly interact to promote function within their cells of origin.