Intra-articular injections of high molecular hyaluronic acid (1% solution) were given at 1- or 2-week intervals to 43 patients with osteoarthritis of the knee. Of the 45 treated knees, 32 (71%) responded favorably. This therapy was effective if the osteoarthritis was of a grade less than moderate; it was not effective in cases with considerable effusion or in those with gross architectural changes. No serious side effects were encountered. We suggest that the beneficial effects of hyaluronic acid may be attributable to improved lubrication of the affected joint, to normalization of synovial fluid production by the action of hyaluronic acid on synovial tissue, and/or to the improvement of the intra-articular environment by the contribution of hyaluronic acid to the rebuilding of the barrier that protects the synovial membrane and articular surface.