The effect of local application of various solutions on leucocyte adherence to the wall of small blood vessels in the microcirculation of the rat mesentery was examined. Leucocyte adhesion was produced by local application of zymosan-activated complement. Solutions of EDTA, lignocaine and prostacyclin when applied locally cause the release of a high proportion of leucocytes previously firmly adherent to the endothelium of venules and small veins without producing any significant change in the rate of blood flow through the affected vessels. Acetylcholine injected intravenously increases the rate of blood flow through the mesenteric microcirculation several fold but has no apparent effect on pre-existing leucocyte sticking. The findings suggest that in normal small blood vessels production of prostacyclin by vascular endothelium may inhibit adhesion of leucocytes to the vascular wall. When endothelium is injured local production of prostacyclin may be inhibited sufficiently to permit adhesion of leucocytes to the injured endothelium and so induce the earliest stage in the emigration of leucocytes into the area of injury. Lignocaine may possibly inhibit leucocyte sticking by increasing local production of prostacyclin, but the mode of action of EDTA and many other aspects of the mechanism responsible for leucocyte sticking remain obscure.