Periprosthetic macrophages were isolated from the synovium of primary and revision arthroplasty patients. Inflammatory activity was determined by the level of superoxide (O2-) production de novo and in response to phorbol myristate acetate (PMA) stimulation. Nonstimulated primary arthroplasty-derived macrophages produced 2.54 +/- 2.04 pmoles of O2-/minute/10(5) cells. When identical reaction tubes were stimulated with PMA, O2- levels increased to 5.76 +/- 3.77 pmol of O2-/minute/10(5) cells. Nonstimulated revision arthroplasty-derived macrophages produced 3.26 +/- 2.02 pmol of O2-/minute/10(5) cells during this ten-minute time period. When identical reaction tubes were stimulated with PMA, O2- levels increased to 3.98 +/- 2.52 pmol of O2-/minute/10(5) cells. The difference in the ratio of O2- production in response to stimulation between primary and revision groups was statistically significant. The observation of a chronic moderate level of activation and the lack of responsiveness to a potent stimulator suggests that macrophage inflammatory activity is down-regulated in periprosthetic synovium.