OBJECTIVE To evaluate plasma dehydroepiandrosterone sulphate (DHEAS) levels in patients diagnosed with age-related macular degeneration (AMD) and controls. METHODS Case-controlled, prospective, comparative noninterventional study. METHODS This study involved 32 men and 35 women with exudative AMD, 37 men and 38 women with nonexudative AMD, and 32 men and 32 women of an age-matched control group. The Wisconsin Age-Related Maculopathy Grading System was used to asses the severity of AMD lesions. DHEAS levels were measured and compared according to a gender based subdivision. Analysis of variance was used to assess the association between DHEAS and AMD. Linear regression model was used to examine the relation among DHEAS level and AMD severity scale. RESULTS Mean +/- SD of DHEAS levels in exudative AMD, nonexudative AMD, and controls in men was 2.67 +/- 0.68 micromol/l, 2.89 +/- 0.95 micromol/l, and 4.43 +/- 1.44 micromol/l, respectively (P = .001), and in women was 1.64 +/- 0.72 micromol/l, 1.85 +/- 0.73 micromol/l, and 2.78 +/- 0.91 micromol/l, respectively (P = .001). Post hoc Tukey analyses revealed a significant reduction in serum DHEAS level in both AMD groups, compared with controls for men and women (P = .001), while no difference was found between AMD groups in both men and women (P = .668 and 0.49, respectively). Regression analyses revealed an inverse correlation among serum DHEAS level and AMD severity scale both in men and women (P = .006 and .007, respectively). CONCLUSIONS This study suggests an inverse correlation between serum DHEAS level and AMD severity scale with a considerably reduced DHEAS level in AMD.