The measurement of plasma total cholesterol as a screening test for an increased plasma level of low density lipoprotein cholesterol (greater than age- and sex-adjusted 95th percentile) with a normal plasma triglyceride level (type IIa hyperlipoproteinemia) was assessed in 1325 young subjects, aged 6 to 19 years, from seven North American populations during the years 1972-1976. When the age- and sex-specific 95th percentile for total cholesterol was used as the cutpoint for hypercholesterolemia, almost one third of young subjects with type IIa hyperlipoproteinemia were undetected (false negatives), and 40% of the test results were falsely positive. Ninety-eight per cent of all non-type IIa subjects were correctly identified. Lowering the percentile cutpoint decreased the false negative results but increased the false positive results; increasing the cutpoint had an opposite effect. Females had higher percentile cholesterol values than males; when extrinsic, arbitrary cholesterol cutpoints (175-210 mg/100 ml) for screening were used, there were fewer false negative but more false positive results in the females than in the males. When the prevalence of type IIa hyperlipoproteinemia was increased from 5 to 50%, the false positive tests decreased from 40 to 2%. A two-step screening for hypercholesterolemia did not improve efficiency. The use of plasma total cholesterol as a test for type IIa hyperlipoproteinemia in a general population results in a relatively large number of false positive and false negative tests.