BACKGROUND Despite declines in blood lead levels during the past 20 years, lead exposure continues to be a public health concern. Studies have linked lead exposure with increased risk for diverse health outcomes. Few studies have evaluated the association of lead exposure and mortality in the general population. METHODS To evaluate the association of lead exposure and mortality in the United States, we used the recently released mortality follow-up data for participants of the Second National Health and Nutrition Examination Survey, a national cross-sectional survey of the general population conducted from 1976 to 1980. Survey participants aged 30 to 74 years with blood lead measurements were followed up through December 31, 1992 (n = 4292). RESULTS After adjustment for potential confounders, individuals with baseline blood lead levels of 20 to 29 microg/dL (1.0-1.4 micromol/L) had 46% increased all-cause mortality (rate ratio [RR], 1.46; 95% confidence interval [CI], 1.14-1.86), 39% increased circulatory mortality (RR, 1.39; 95% CI, 1.01-1.91), and 68% increased cancer mortality (RR, 1.68; 95% CI, 1.02-2.78) compared with those with blood lead levels of less than 10 microg/dL (<0.5 micromol/L). All-cause mortality for those with blood lead levels of 10 to 19 microg/dL (0.5-0.9 micromol/L) was intermediately increased and not statistically significant (RR, 1.17; 95% CI, 0.90-1.52). CONCLUSIONS Individuals with blood lead levels of 20 to 29 micro g/dL in 1976 to 1980 (15% of the US population at that time) experienced significantly increased all-cause, circulatory, and cardiovascular mortality from 1976 through 1992. Thus, we strongly encourage efforts to reduce lead exposure for occupationally exposed workers and the 1.7 million Americans with blood lead levels of at least 20 micro g/dL (> or = 1.0 micromol/L).