This study compared the effects of different sizes of three clinically relevant endotoxin free bone cement particles on primary human macrophage TNF-alpha production in vitro. The bone cements used were CMW original, CMW1RO and Palacos R. The cement wear debris was generated aseptically and then sequentially filtered to produce the size ranges 0.1-1 microm, 0.1-10 microm, 1-10 microm and >10 microm. The debris was cultured with human peripheral blood mononuclear cells at particle volume (microm(3)) per cell ratios of 100:1, 10:1 and 1:1. TNF-alpha production was determined by ELISA and cell viability by MTT conversion. CMW1RO particles induced increased TNF-alpha production by PBMNCs when tested in the size range 0.1-1 microm, and also to a lesser degree in the sizes 0.1-10 microm and 1-10 microm at the particle volume (microm(3)) to cell number ratios of 100:1 and 10:1. The increase in TNF-alpha production induced by Palacos R debris was only observed with the particle size ranges less than 10 microm at the ratio of 100:1. This study demonstrated that bone cement particles are capable of inducing raised TNF-alpha production in vitro. This is dependent upon cement particle size, volume and cement particle type, with cement particles containing radio-opaque additives being the most active.