The foveal region of the retina has a yellow pigmentation composed primarily of the carotenoids lutein and zeaxanthin. Past studies have shown that cigarette smoking depresses carotenoid concentrations in the blood. This is the first report on the effects of cigarette smoking on carotenoids in the retina. Macular pigment optical density (MP) was measured psychophysically by comparing foveal and parafoveal sensitivities to light of 460 and 550 nm. General dietary patterns, smoking frequency (cigaretts/day) and personal data were collected by questionnaire. Thirty-four smokers and 34 nonsmokers were compared. Subjects were matched with respect to age, sex, dietary patterns and overall pigmentation (i.e., eye, skin and hair color). The smoking group had a mean MP of 0.16 (SD = 0.12) compared to a mean MP of 0.34 (SD = 0.15) for nonsmokers (P < 0.0001). MP density and smoking frequency were inversely related (r = -0.498 P < 0.001) in a dose-response relationship. A variety of evidence suggests that MP protects the macula from actinic damage both passively (by screening potentially harmful short-wave light) and actively as an antioxidant (e.g., by quenching reactive oxygen species). If smoking causes a reduction in MP density, then smokers may be at risk. Epidemiologic data identifying smoking as a risk factor for the neovascular form of age-related macular degeneration are consistent with this hypothesis.