We studied the relationship between eight variables, including age, sex, baseline plasma beta-carotene (BC) concentration, and smoking status and the increase in plasma BC in 582 subjects receiving oral supplementation with 50 mg BC/d. Median plasma BC concentrations after 1 y of supplementation increased from 335 nmol/L at entry to 3163 nmol/L. Changes in plasma BC concentrations ranged widely from -313 to 16,090 nmol/L (median 2721 nmol/L). Multivariate analysis revealed that the subject's plasma BC concentration before supplementation was the most important indicator of the amount of increase after supplementation. Nonsmokers, women, and leaner subjects all had larger increases in plasma concentrations although the statistical model could account for relatively little of the variability in subjects' plasma response to BC supplementation (R2 = 0.14). We conclude that between-subject variability in response to daily supplementation with oral BC is very large and that the best predictor of this response is the initial plasma BC concentration.