Although tissue culture techniques are used extensively to explore the biocompatibility of various biomaterials used in orthopaedic, dental and pharmaceutical fields, the role of these materials towards human monocytes/macrophages has not been fully elucidated. The specific objectives of this investigation were: (1) to determine the biochemical markers resulting from exposure of the human monocytes/macrophages to titanium (TI), large size polyethylene (LSP), submicron polyethylene (SPE), hydroxyapatite (HA), large particle size tricalcium phosphate (LTCP), and small particle size tricalcium phosphate (STCP), and (2) to morphologically evaluate the viability of the cells treated with the aforementioned biomaterials. Approximately 15 volunteers donated blood for each phase (24, 48, and 72 hours) of the experiment. The monocytes were isolated by following established lab procedures (Histopaque 1077 and 1119). Aseptic techniques were followed throughout each phase. Each phase contained four experimental groups (TI, LSP, SPE, HA). Each group was comprised of six wells. The total protein, catalase, LDH, MDA, and cell count were measured using established lab protocols. Data obtained suggests that: (I) regardless of the biomaterial being used all experimental groups experienced remarkable phagocytosis in the first two phases (24, 48 hours), (II) during the 24 hour phase MDA activities were increased in TI, LTCP, and STCP treated wells when compared to the control and other experimental groups, (III) in the 48 hour phase the MDA level increased in LPE and STCP treated cells, (IV) there were significant differences in LDH levels in LPE, STCP, and SPE at 24 hours compared to the control and other experimental groups, (V) LDH activities were increased in LPE, STCP, SPE, and LTCP at 48 hours, and (VI) at 72 hours there were significant increases in catalase activity in HA, TI, SPE and LPE when compared to the control group and other experimental groups. Information obtained from this study provided new ideas about the interrelationship of various biomaterials, the effect of size and cell response to the various biomaterials.