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The aim of our study was to test the hypothesis that differences in behavioral characteristics are linked to severity of arthritis in association with neuro-endocrine and immune reactivity in an inbred strain of rats. Lewis rats were selected as high-active (HA) and low-active (LA) animals based on their exploratory activity in the open field. Subsequently, adjuvant-arthritis (AA) was induced in both groups. We observed no differences in the severity of inflammation as determined by paw swelling and redness. However, LA and HA animals differed in the severity of bone destruction as determined on radiographs taken on day 30 after induction of AA. LA rats had more osteoporosis, periostal new bone formation, and bone destruction than HA rats. There were no differences between HA and LA rats in corticosterone response after acute or chronic immune challenge. Splenocytes of LA rats had a lower mitogen-induced IL-10 and IFNgamma production during AA. Histological examination revealed more intense factor VIII staining in arthritic joints of LA animals, indicating more pronounced synovial angiogenesis. In addition, LA rats had higher plasma VEGF, an important angiogenic factor. Expression of RANKL, a crucial factor promoting bone resorption, was also higher in joints of LA animals. Our data demonstrate that activity in the open field, a behavioral trait, is associated with the severity of bone destruction in AA. Lower production of bone-protective cytokines and a higher rate of angiogenesis leading to more synovial proliferation may be responsible for the more severe joint destruction in LA animals.