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Senile macular degeneration, although a leading cause of visual loss in the United States, remains a poorly understood disease. To assess the effects of host and environmental factors on this condition, a study of 228 cases and 237 controls matched by age and sex, who had visited any of 34 Baltimore ophthalmologists between September 1, 1978 and March 31, 1980, was conducted. Study participants were interviewed for past medical, residential, occupational, smoking and family histories, as well as social and demographic factors. Diagnoses were validated by means of fundus photographs. The 162 cases and 175 controls who met the study diagnostic criteria for cases and controls were included in the analysis. Statistically significant associations were demonstrated between senile macular degeneration and family history of macular disease (odds ratio (OR) = 2.9), chemical work exposures (OR = 4.2), blue or medium pigmented eyes (OR = 3.5), history of one or more cardiovascular diseases (OR = 1.7), decreased hand grip strength, and hyperopia. The risk of macular degeneration in cigarette smokers was significant for males only (OR = 2.6). The study results suggest that the development of macular degeneration is mainly influenced by familial, genetic, and personal characteristics, rather than by the few environmental factors studied. Additional studies are needed to further evaluate the role of environmental factors.