There has been increasing use of high-dosage zinc supplementation in the population, in particular as a potential treatment for age-related macular degeneration. We examined the relationship between fasting serum zinc and serum lipid levels in 778 adults, aged 22 to 80 years, who were control subjects in a multicenter, clinic-based case-control study. The samples were taken during 1987 to 1990, a time when vitamin/mineral supplementation was becoming increasingly common. We found that higher serum zinc levels, most notably those above the highest quintile, were associated with higher levels of total serum cholesterol, low-density-lipoprotein cholesterol, and triglycerides. No significant trend was noted for high-density-lipoprotein cholesterol. Previous studies demonstrated that high-dosage zinc supplements raise serum zinc levels. The possibility that use of such supplements can adversely affect serum lipid profiles suggests that chronic ingestion of such supplements should not be done without adequate medical supervision.