The in vitro response of peripheral blood mononuclear cells (MNC) from patients with cemented total hip or knee arthroplasties, and control individuals, to polymethylmethacrylate (PMMA) was assessed by cell proliferation, cytokine production, and molecular techniques. After seven days in culture, a dose-dependent proliferative response to PMMA stimulation was observed in MNC from fifteen normal individuals. A concomitant dose-dependent production of both IL-1 beta and IL-2 in response to PMMA stimulation was detected. Reverse transcription-polymerase chain reactions (RT-PCR) indicated that both IL-1 beta and IL-2 mRNA was present after 48 hours in culture with PMMA. Cellular proliferation and cytokine production (both IL-1 beta and IL-2) in 10 patients with stable, painless, well-functioning, cemented arthroplasties was significantly lower (p < 0.025) than normal controls and patients with aseptically loosened, painful, arthroplasties. The findings suggest that patients with stable cemented total joint arthroplasties are either inherently or adaptively less responsive to PMMA at a cellular level.