Objectives: The intra-and interindividual variations and season and center effects were estimated from a series of serum carotenoid concentrations in the Polyp Prevention Trial (PPT) participants. Subjects/Methods: Fasting blood was collected annually for 4 years in all 1905 participants, and a subcohort of 901 participants were selected within each (of eight) center(s), by gender and dietary arm of the study, for measurement of five major carotenoid peaks. Using variance of component methods, the variation in serum carotenoid concentrations about the underlying mean was partitioned into explanatory components attributed to various sources. Results: The contributions of the inter-and intraindividual variances to the overall variation in carotenoid concentrations were in the range of 61-70 and 20-35%, respectively, whereas center and center-by-season effects provided 2.6-9.5 and 0.2-1.4%, respectively. The highest percent (35%) of intraindividual variation was exhibited by lycopene, and the highest percent (70% apiece) of interindividual variation was exhibited by lutein/zeaxanthin and b-carotene. Serum lycopene had the highest ratio of intra-to interindividual variation of 0.57, whereas lutein had the lowest ratio of 0.29. We estimate that the ratio of intrato interindividual variance around the mean carotenoid concentration can be reduced greatly by collecting 3-4 compared to 1 blood measurement in large-scale trials like the PPT. Conclusion: In the largest study of components of variation in individuals at high risk for colorectal cancer, the largest contributors to variation in serum carotenoid concentrations were intra-and interindividual effects followed by center and center-by-season effects.