Type II collagen-induced arthritis is a pathologic process mediated, in part, by humoral immune mechanisms. Because many antibody-mediated reactions are neutrophil-dependent, the role of this cell population was examined in collagen arthritis. In rats depleted of neutrophils with rabbit anti-rat neutrophil antiserum (ANS), swelling and inflammation associated with the arthritis response were maximally reduced by 65% (P less than 0.001). ANS treatment had no detectable effect on delayed hypersensitivity or antibody response to Type II collagen. Also, levels of peripheral blood monocytes, lymphocytes, and platelets were unaffected. Treatment with normal rabbit serum (NS) had no detectable effect on any of the inflammatory or immune parameters tested nor on circulating levels of monocytes, lymphocytes, or platelets. These results suggest that further study of the functions of neutrophils in rat collagen arthritis may be of help in our understanding of the role of this cell population in human arthritis.