Fungal infection is a rare but devastating complication of total joint arthroplasty. Many patients require removal of the components and resection arthroplasty for cure; however, revision arthroplasty with medicated polymethylmethacrylate bone cement may be used to salvage the joint. Some studies have documented the efficacy of mixing antibiotics with polymethylmethacrylate, but the efficacy of antifungal drugs when mixed with polymethylmethacrylate is unknown. An in vitro agar diffusion method was used in the current study to investigate this potential, and several clinically important conclusions resulted: (1) after incorporation into bone cement, fluconazole and amphotericin B remained active whereas 5-flucytosine did not, (2) inhibitory activity improved with greater drug concentrations, and (3) more drug eluted from Palacos R than Simplex P cement.