U sing a new in vitro method of measuring the chemotaxis of polymorphonuclear leukocytes from peripheral blood, a chemotactic index has been calculated. The mean chemotactic index of 320 in 24 patients with definite rheumatoid arthritis, was significantly less (P < 0.0005) than the mean of 555 in 24 normal controls matched for age and sex.The mean chemotactic index of 435 in eight patients with juvenile rheumatoid arthritis was also significantly less (P < 0.01) than that of 553 in similarly matched controls.The chemotactic index could not be correlated with age, sex, disease activity, drugs used in treatment, latex titer, immunoglobulin levels, or protein coating on the cells. However, there was a correlation between the chemotactic index and the serum complement B_1e/B_1a value (P < 0.01) in 17 patients with adult onset rheumatoid arthritis. Although the serum complement B_1e/B_1a values were within the normal range, the lowest chemotactic indices were associated with the lowest complement values.The chemotactic indices in three patients with severe connective tissue disease (seropositive rheumatoid arthritis, systemic lupus erythematosus, and polymyositis) returned to normal after 5 days' treatment with 60 mg of prednisolone per day. Incubation of the cells from patients with rheumatoid arthritis with hydrocortisone in vitro failed to alter the chemotactic indices.Prior incubation of normal cells with purified rheumatoid factor complexes, rheumatoid serum, or macromolecules of iron dextran impaired their chemotaxis. It is suggested that phagocytosis of complexes in vivo is a possible mechanism by which the chemotaxis of the polymorphonuclear leukocytes of patients with rheumatoid arthritis is impaired.This impairment in chemotaxis may explain the increased incidence of bacterial infection, both during life and as a cause of death in these patients.