The National Cholesterol Education Program has begun a National Campaign to screen millions of adult Americans for serum cholesterol. To determine whether such random samples represent an individual's true lipoprotein status, we measured fasting total serum cholesterol and lipoproteins, on a weekly basis for 4 weeks, in 20 subjects ages 22 to 63 years. Duplicate samples were tested by two standardized laboratories, each on five consecutive days. Variations of more than +/- 20% in the serum levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were seen in 75%, 95%, and 65% of the subjects, respectively. On retesting, 40% of the subjects moved in or out of one "risk category"; and in 10% two categories, from "desirable" to "high risk," or vice versa. These data demonstrate that random testing may fall to detect wide fluctuations in the levels of serum lipoproteins, and therefore result in erroneous risk assignment or therapeutic intervention.