The effect of synthetic amphiphiles, poly(ethyleneglycol) 6000 (PEG) esterified with saturated fatty acids (C2-C18), on the locomotion of polymorphonuclear leucocytes (PMNL) has been investigated. It was noticed that PEG-myristate (M-PEG; C14) stimulated the random locomotion of PMNL populations in concentrations up to about 1 g/l. By contrast, the esters with shorter aliphatic chains had negligible effects and those with longer chains, PEG-palmitate (P-PEG; C16) and PEG-stearate (S-PEG; C18) reduced the locomotion, irrespectively of concentration. The ability of the PMNL to be stimulated by an attractant liberated from normal human serum was slightly impaired with M-PEG, but not with P-PEG. The response to M-PEG of individual PMNL was heterogeneous in that some cells were stimulated and others were inhibited, but the average result was a reduction of the motility. This indicates that methods used for the study of the locomotion of cell populations do not always reproduce the true behaviour of the whole population, but rather of a selected subpopulation. It was also concluded that the different effects of M-PEG and P-PEG were probably not due to phagocytosis or selective binding of either substance, but rather due to dissimilar effects on the membrane structure of the PMNL, since (i) M-PEG perturbated the PMNL membrane more than P-PEG, as assayed by the release of superoxide anion (O2-) although the binding was smaller, and (ii) M-PEG and P-PEG increased and decreased the membrane fluidity, respectively, as measured with fluorescence bleaching and recovery after bleaching of labeled PMNL. The results indicate a subtle coupling between membrane structure and PMNL locomotion.