In this case-control study we determined whether dietary differences underlie some of the ethnic and sex differences in US lung cancer rates. We examined the relationship between diet and lung cancer development in 137 lung cancer cases (93 African Americans and 44 Mexican Americans) and 187 controls (78 African Americans and 109 Mexican Americans). Cases reported a higher daily mean total fat intake (p < 0.001), whereas controls had a higher daily mean intake of dietary fiber (p < 0.001) and fruits (p = 0.02). Ethnic differences in diet were also observed: Mexican Americans consumed less total fat (p < 0.02) and more fiber (p < 0.001) and vegetables (p = 0.08) than African Americans. Additionally, men consumed more total fat (p = 0.08) and less fiber (p = 0.001), fruits (p < 0.001), and vegetables (p = 0.002) than women. Multivariable analysis, after adjustment for the effects of pack-years of smoking, age, total energy intake, sex, and ethnicity, demonstrated a positive association between high total fat consumption and lung cancer risk (p < 0.01) and an inverse association between high fruit consumption and lung cancer risk (p = 0.05). In conclusion, our findings support the hypothesis that diet, particularly high fat consumption and low fruit and vegetable consumption, contributes (independent of cigarette smoking) to the excess lung cancer risk in African-American men, who have the highest lung cancer rates in the United States.