1. Lipoxin A 4 (LXA 4 ) and lipoxin B 4 (LXB 4 ) have been evaluated for their capacities to modulate neutrophil (PMN) migration and endothelial cell adherence using compounds prepared by total chemical synthesis. 2. Increased PMN migration was seen with concentrations of LXA 4 from 10 −9 mol/l to 10 −7 mol/l. LXA 4 was 100-fold less potent than leukotriene B 4 (LTB 4 ) and it elicited only one-half of the maximal response of LTB 4 . 3. The (5 S ,6 S ,15 S )-isomer of LXA 4 induced only a weak migratory response and LXB 4 was inactive, suggesting that the activity of LXA 4 was stereospecific. 4. Modified chequerboard analysis indicated that LXA 4 was a chemokinetic agent. 5. Preincubation of PMN with increasing concentrations of LXA 4 induced a very similar dose- and time-dependent inhibition of the subsequent response to 10 −7 mol/l LTB 4 or 10 −7 mol/l N -formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP). The inhibition was observed at 10 −10 mol/l LXA 4 ; the concentration which produced 50% inhibition was 10 −8 mol/l and 100% inhibition of PMN locomotion occurred at 10 −6 mol/l LXA 4 . 6. The (5 S ,6 S ,15 S )-isomers of LXA 4 and LXB 4 were 5- and 100-fold less potent than LXA 4 , respectively, in suppressing LTB 4 - or FMLP-induced PMN migration. 7. Preincubation of PMN with LXA 4 led to a suppression of calcium mobilization, as assessed by Quin2-AM fluorescence, when the cells were subsequently stimulated under optimal conditions by LTB 4 or FMLP. 8. These results suggest that the inhibitory activity of lipoxins may be related to the capacity of these molecules to regulate calcium ion mobilization. 9. LXA 4 and LXB 4 did not promote PMN adherence to human endothelial cell monolayers and they did not modulate FMLP-stimulated PMN-endothelial cell adhesion.