We report on the location and skewness of the distribution of plasma total homocysteine (tHcy) according to lifestyle indexes in 11,941 apparently healthy participants of the Hordaland Homocysteine Study. Most subjects were in two age groups: 9165 subjects were aged 40-42 y and 2351 subjects were aged 65-67 y. The remaining 425 subjects were of intermediate ages. In multivariate analysis, sex, age, folate intake, smoking status, and coffee consumption were the strongest determinants of tHcy concentration. The combined effect of the three modifiable factors was larger than the effect from each factor alone. A lifestyle profile characterized by low folate intakes, smoking, and coffee consumption was associated with a high median tHcy concentration and a pronounced skewness toward high tHcy values. In subjects characterized by a contrasting lifestyle profile [high folate intakes, nonsmoking status, and low coffee consumption (< 1 cup/d)], tHcy values were almost normally distributed and the median concentration was 3.0-4.8 micromol/L lower. Among all 40-42-y-old subjects, the 95% reference ranges based on geometric mean tHcy concentrations were 5.1-16.5 micromol/L for women and 6.2-18.7 micromol/L for men. The corresponding ranges for subjects characterized by high folate intakes, nonsmoking status, and low or moderate coffee consumption (< 5 cups/d) were 4.8-12.8 micromol/L and 6.2-14.7 micromol/L. These findings are relevant for establishing adequate reference ranges for tHcy and emphasize folate intake, smoking status, and coffee consumption as major acquired determinants of tHcy concentration in this general population.