The fundamental role played by macrophages and fibroblasts of the synovial-like membrane in aseptic hip prosthesis loosening (AHPL) has recently been confirmed by numerous studies. In this study, the activity of these cells in patients with prosthetic loosening was analyzed by evaluating the main markers of fibroblast and macrophage activation in sera and in supernatants of cultured fibroblasts obtained from AHPL patients who underwent revision of a loose total hip arthroplasty implant. In these patients interleukin-1, hyaluronic acid (HA), and type III procollagen peptide were evaluated. The results were compared with those obtained in 13 patients with firmly fixed implants and 13 patients with osteoarthritis. Serum HA levels were significantly higher (779.3 +/- 951.6 micrograms/L) in patients with AHPL as compared with patients with firmly fixed implants (112.9 +/- 84.9 micrograms/L) and osteoarthritis (115.3 +/- 107.8 micrograms/L). Type III procollagen peptide levels were elevated in only 33.3% of patients with AHPL, whereas interleukin-1-beta (IL-1 beta) was detectable in 4 patients with AHPL but not in patients with firmly fixed implants or osteoarthritis. In supernatants, IL-1 beta was measurable in 4 of 6 fibroblast cultures, whereas type III procollagen peptide and HA were measurable in all cultures. The data confirm the existence of an inflammatory process in AHPL patients in which macrophages and fibroblasts play a key role. The detection, in these patients, of high circulating levels of IL-1 beta and HA is very important from a clinical point of view because they could be considered specific markers of inflammation.