Fourteen patients with rheumatoid arthritis (RA) were studied before, during, and after a 1-week total fast. Disease activity decreased, as did the neutrophil release of lysozyme induced by the ionophore A23187. The ability of zymosan-activated RA patient serum to aggregate control neutrophils was reduced, together with serum concentrations of C3. The relative contents of arachidonic acid and eicosapentaenoic acid were increased in serum, platelets, and neutrophils, whereas levels of linoleic acid and linolenic acid were unchanged. Fasting also reduced the release of leukotriene B4 from neutrophils. We thus conclude that a reduced ability to generate cytotaxins, reduced release of enzyme, and reduced leukotriene formation from RA neutrophils, together with an altered fatty acid composition of membrane phospholipids, may be mechanisms for the decrease of inflammatory symptoms that results from fasting.