The pathophysiologic significance of leukotriene B4 (LTB4) in arthritis was studied in dogs by unilateral intraarticular deposition of 15-hydroxy-eicosatetraenoic acid (15-HETE), an endogenous inhibitor of the formation and the effects of LTB4, in bilateral carrageenan-induced gonarthritis. LTB4 in synovial fluid was selectively inhibited in 15-HETE treated joints, the formation of prostaglandin E2 (PGE2) being largely unaffected. The clinical symptoms, intraarticular pressure, and extractable synovial fluid volume were reduced in treated joints. No effect could be discerned regarding blood flow in the synovial membrane, capsule, or juxta-articular bone as measured by tracer microspheres; and no effect on bone metabolism was found as judged by 99mTc-diphosphonate uptake. Thus, inhibition of LTB4 reduces joint exudation, but does not seem to interfere with changes in juxta-articular hemodynamics or bone metabolism following synovial inflammation.