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 carragheenan-induced gonarthritis. LTB₄ in synovial fluid was selectively inhibited in 15-FETE 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 juxtaarticular 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 juxtaarticular hemodynamics or bone metabolism following synovial inflammation.