To confirm a reported association between elevated serum albumin concentrations and reduced risk of death in middle-aged white men and to determine whether such associations exist for CHD incidence in white men and CHD and death in white women and black men and women, data were examined from the NHANES I Epidemiologic Follow-up Study. Over a follow-up period of 9 to 16 years, serum albumin concentrations of 4.5 gm/dl or more were associated with reduced risk of CHD incidence in white men aged 45 to 64 years (RR = 0.51; 95% CL = 0.36, 0.73) and in white women aged 45 to 74 years (RR = 0.70; 95% CL = 0.55, 0.88), independent of baseline risk factors. Independent reductions in risk of death from all causes, cardiovascular diseases, and noncardiovascular diseases were also seen in white men and women. Relative risk of death from all causes at ages 45 to 74 years in the white population was 0.73 (95% CL = 0.62, 0.85) for men and 0.71 (95% CL = 0.59, 0.85) for women. Similar reductions in risk of death from all causes and cardiovascular diseases were seen in black men and women, despite the small numbers. Further studies are needed to confirm these findings for women and black persons and to elucidate mechanisms for the effect of serum albumin.