The influence of pregnancy serum on the directional migration of normal human polymorphonuclear leukocytes (PMN) in response to a standard chemotactic attractant was studied. Using the Boyden chamber method for quantitating directional migration, both gestational and control sera in the unmodified state were found to have comparable actions on neutrophil chemokinesis and chemotaxis. Activation of these sera with endotoxin generated equivalent amounts of chemotactic factors. However, pregnancy serum in direct contact with normal PMN, inhibited their response to a standard chemoattractant (p less than 0.001). The suppressive effect was present in sera obtained during the third trimester of gestation. Sera obtained one month post partum contained less of the inhibitor of PMN directional migration. Since neutrophils are essential to the development of rheumatoid arthritis and certain other inflammatory diseases, the subsidence of these disorders during gestation and their exacerbation post partum could be related to the inhibitory effects of pregnancy serum on leukocyte functions.