The pathogenesis of reactive arthritis is multifactorial. The possible pathogenetic mechanisms include the role of microbial antigens which cross-react with the host tissue or trigger cytotoxic immune response. In addition an exaggerated inflammatory response of the host may contribute to the clinical picture of the acute arthritis and its late sequels. In this review, we present data showing that HLA-B27 positive subjects show enhanced neutrophil (PMN) migration and their sera support PMN migration more than HLA-B27 negative sera. Enhanced PMN function is persistent in patients with previous severe reactive arthritis or with late inflammatory sequels. In addition to hyperreactive PMNs, monocytes from patients with previous yersinia arthritis, but also from healthy HLA-B27 positive subjects, respond to stimulation with lipopolysaccharide by enhanced production of inflammatory monokines compared with HLA-B27 negative healthy controls. Thus, hyperreactive phagocytes can contribute to the severe inflammatory complications seen in patients with reactive arthritis. The primed phagocytes can also respond vigorously when stimulated either with endogenous mediators of inflammation or with endotoxin released during a new infection or as a sequel of change in the mucosal permeability described in patients with spondyloarthropathy.