BACKGROUND AND PURPOSE: Metal ion toxicity both locally and systemically following MoM hip replacements remains a concern. Cobalt ions have been shown to induce secretion of proinflammatory chemokines locally; however, little is known about their effect systemically. We investigated the in vitro effect of cobalt ions on a variety of cell lines by measuring production of the proinflammatory chemokines IL-8 and MCP-1. METHOD: Renal, gastrointestinal, and respiratory epithelium and also neutrophils and monocytes were exposed to cobalt ions at 4, 12, 24, and 48 hours. RESULTS: We found that cobalt ions enhanced the secretion of IL-8 and MCP-1 in renal epithelial cells, gastric and colon epithelium, monocytes and neutrophils, and small airway epithelial cells but not in alveolar cells. Secretion of IL-8 and MCP-1 was markedly elevated in renal epithelium, where a 16-fold and 7-fold increase occurred compared to controls. There was a 6-fold and 4-fold increase in IL-8 and MCP-1 secretion in colon epithelium and a 4-fold and 3-fold increase in gastric epithelium. Small airway epithelial cells showed a maximum increase in secretion of 8-fold (IL-8) and of 4-fold (MCP-1). The increase in chemokine secretion observed in alveolar cells was moderate and did not reach statistical significance. Monocytes and neutrophils showed a 2.5-fold and 2-fold increase in IL-8 secretion and a 6-fold and 4-fold increase in MCP-1 secretion at 48 and 24 hours, respectively. INTERPRETATION: These data demonstrate the potent bioactivity of cobalt ions in a variety of cell types and the potential to induce a proinflammatory response.