Both LTB4 and AGEPC stimulate PMN aggregation in a concentration-dependent manner. The lipoxygenase inhibitors ETYA and NDGA block AGEPC-induced but not LTB4-induced PMN aggregation. Agents that elevate PMN cyclic AMP levels block both LTB4-and AGEPC-induced aggregation. Paradoxically, shortly after aggregation is initiated by either AGEPC or LTB4, a transient spike in cyclic AMP levels is observed. Subsequent experiments show that LTB4 can directly elevate cyclic AMP in PMNs. Reverse-phase high-pressure liquid chromatography, coupled with selective ion gas chromatography/mass spectrometry, shows that AGEPC stimulates neutrophils to synthesize LTB4. These data suggest that AGEPC-induced neutrophil aggregation is mediated by LTB4.