Antiflammins are synthetic peptides corresponding to a region of similarity between uteroglobin and lipocortin I. These peptides inhibit synthesis of platelet-activating factor and release of arachidonic acid from neutrophils and macrophages stimulated by phagocytosis or tumor necrosis factor. Antiflammins containing methionine are inactivated readily in the absence of reducing agents. Novel antiflammins containing alanine or norleucine in place of methionine are inhibitory without added reducing agents, but only when stock solutions are heated to 45 degrees C. Heating may favor hydrophobic interactions between peptide molecules, thereby activating the antiflammins. These peptides are less inhibitory when added after cell stimulation, suggesting that they interfere with the activation of phospholipase A2.