Titanium (Ti) and copper (Cu) were used to evaluate cytokine secretion around materials with different chemical properties. Ti disks were coated with Cu or left uncoated. The disks were inserted subcutaneously in rats for 1, 3, 12, 18, 24 and 48h. Interleukin-1a (IL-1a), IL-1ß and tumor necrosis factor-a (TNF-a) concentrations were measured in vivo around the materials, in sham operated sites, and after ex vivo incubation of surface adherent cells. Ti and Cu revealed distinct cytokine expression patterns. Cu recruited cells showed higher and prolonged release of IL-1a than Ti at longer times (>24h), whereas Ti exhibited a transient IL-1a response at earlier periods (<24h). An early enhanced secretion of TNF-a characterized Ti. Low amounts of IL-1ß were found around both materials. Sham site recruited cells produced lower levels of cytokines. The results after ex vivo incubations were similar to those in vivo. This study shows that material chemical properties influence early cytokine production. The Ti-associated transient rise of IL-1a and TNF-a may be of importance for the early tissue response around biocompatible materials, while a delayed high IL-1a expression could be a marker of inflammation induced by toxic materials. © 2002 Elsevier Science Ltd. All rights reserved.