Neutrophils from healthy volunteers were isolated and incubated with varying concentrations of albumin-bound long chain free fatty acids. Standard in vitro function tests including phagocytosis, bactericidal activity, and chemotaxis were performed after the incubation. It was found that unsaturated fatty acid (oleic acid) caused no changes in bactericidal activity and only moderate decreases in phagocytosis and chemotaxis at very high concentrations. Saturated fatty acid (palmitic acid) produced, at high concentrations, virtually complete inhibition of chemotaxis and moderate depression of phagocytosis and bactericidal ability. Most significantly, lower concentrations of saturated free fatty acids, within the range reported clinically in various diseases, caused a marked inhibition of chemotaxis. These functional disturbances were associated with ultrastructural alterations. Neutrophils treated with oleic acid contained numerous cytoplasmic neutral lipid droplets. Neutrophils incubated with palmitic acid showed elongated cleftlike dilations of the endoplasmic reticulum and degenerative degranulated cytoplasmic areas. It is postulated that these represent crystallization of excess saturated free fatty acids or triglyceride which interfere with chemotaxis, either mechanically or by causing cell injury.