Type II collagen-induced arthritis (CIA) 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 passive CIA transferred with anti-type II collagen (CII) antibody. In cyclophosphamide (CY)-induced leukocytopenic rats, swelling and inflammation associated with the arthritic response were significantly reduced. Concomitant administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to leukocytopenic rats for 7 consecutive days from the day of CY injection resulted in the recovery of peripheral blood neutrophils count and the abrogation of the suppression of arthritis with an optimal dose of anti-CII antibody. Further study demonstrated that a prior administration of rhG-CSF to naive rats for five consecutive days resulted in the significant and specific increase of peripheral blood neutrophils count and enhancement of passive arthritis with a suboptimal dose of anti-CII antibody. It was suggested that neutrophils played an important role in the development of passive CIA.