Hyaluronans are used widely in the treatment of osteoarthritis of the knee. Three commercial hyaluronan preparations currently are available in the United States: sodium hyaluronate (Hyalgan), sodium hyaluronate (Supartz), and hylan G-F 20 (Synvisc). Although the sodium hyaluronates are derived naturally, hylan is chemically modified to increase its molecular weight. All three products have been shown to be well tolerated in clinical trials, however, there have been reports in the literature of pseudoseptic reactions, or severe acute inflammatory reactions, after injections with hylan. Our study reviewed the reported incidence of pseudosepsis. The pathogenic mechanisms and clinical treatment of this reaction are presented.