Objective: To evaluate the activation state of macrophage function in patients with age-related macular degeneration (AMD) by quantifying the production of t he proinflammatory and angiogenic factor tumor necrosis factor α(TNF-α) and b y correlating its expression with dry and wet AMD. Methods: Circulating monocyte s were obtained from the blood of patients with AMD or age-matched control subj ects by gradient centrifugation. The monocytes were then analyzed for either TNF -αrelease from cultured macrophages in response to retinal pigment epithelium -derived blebs and cytokines or TNF-αmessenger RNA content by reverse transcr iptasepolymerase chain reaction. Results: In human monocytes obtained from contr ols and AMD patients, TNF-αwas expressed by freshly isolated monocytes and pro duced by macrophages in culture after stimulation with retinal pigment epitheliu m-derived blebs. However, wide variability in TNF-αexpression was observed am ong different patients. Patients with monocytes that expressed the greatest amou nt of TNF-αdemonstrated higher prevalence of choroidal neovascularization. Con clusions: Both controls and AMD patients vary in the activation state (defined a s TNF-αexpression) of circulating monocytes. Partially active monocytes, defin ed as high TNF-αexpression, may be a biomarker to identify patients at risk fo r formation of choroidal neovascularization. Clinical of Relevance: Early diagno stic testing may prove useful to detect those patients who will progress to the more severe complications of the disease. Objective: To evaluate the activation state of macrophage function in patients with age-related macular degeneration (AMD) by quantifying the production of t he proinflammatory and angiogenic factor tumor necrosis factor α (TNF-α) and by correlating its expression with dry and wet AMD. Methods: Circulating monocytes were obtained from the blood of patients with AMD or age-matched control subj ects by gradient centrifugation. The monocytes were then analyzed for either TNF-α release from cultured macrophages in response to retinal pigment epithelium-derived blebs and Results: In human monocytes obtained from controls and AMD patients, TNF-αwas expressed by freshly isolated monocytes and pro duced by macrophages in culture after stimulation with retinal pigment epitheliu m- derived blebs. However, wide variability in TNF-α expression was observed am ong different patients. Patients with mon ocytes that expressed the greatest amou nt of TNF-αdemonstrated higher prevalence of choroidal neovascularization. Con clusions: Both controls and AMD patients vary in the activation state (defined as TNF-αexpression) of circulating monocytes. Partially active monocytes, defin ed as high TNF -αexpression, may be a biomarker to identify patients at risk fo r formation of choroidal neovascularization. Clinical of Relevance: Early diagno stic testing may prove useful to detect those patients who will progress to the more severe complications of the disease.