Controversy remains regarding the ability of silicone materials to induce a specific immune reaction versus a nonspecific inflammatory response. Histopathological analysis of the tissue around failed breast implants reveals chronic inflammation with silicone gel droplets either surrounded by giant cells or engulfed by macrophages, areas of fibrosis, and necrosis. Macrophages are the key cells engulfing or forming foreign body giant cells. To address the mechanisms of silicone-induced inflammation a model of human monocyte-derived macrophages (MDMs) was developed. After sonication of silicone gel, the silicone droplets were embedded in Type I collagen and used to coat glass coverslips; human MDMs were subsequently seeded on the coverslips and maintained in culture for up to 7 days. The advantage of the model was that human macrophages could be studied histologically, and cytochemically as they interacted with well-characterized silicone materials. Initial analysis of the human macrophages shows phagocytosis of the silicone gel within hours of exposure to the material. Analysis for pro-inflammatory cytokines reveals significant transient secretion of IL-1 (p < 0.01) over controls by human macrophages upon exposure to silicone gel at 24 h.