The dependence of cytotoxicity on particles size in titanium (Ti) and nickel (Ni) was investigated by biochemical functional analysis and by microscopic observation of cellular morphology, in vitro using human neutrophils as probes and in vivo in animal implantation test. The biochemical analyses of cell survival rate, LDH, superoxide anion, cytokines of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and observation by scanning electron microscopy (SEM) showed that Ti fine particles (2 \\micron) stimulate neutrophils and increases the quantity of released superoxide anions, whereas Ni particles deform or disrupt the cell membrane of neutrophils. The 2 \\micron Ti particles, smaller than neutrophils of about 5–10 \\micron, were phagocytized by cells in vivo and the results were similar in vitro, which lead to the remarkable release of TNF-α. These results showed that there is the size-dependent cytotoxic effect in Ti fine particles and the effect is the most pronounced when they are smaller than cells. On the other hand, Ni particles caused the disruption of neutrophils in vitro and necrosis of tissue in vivo mainly through ions produced by their dissolution.