The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (1.1.1.34) was measured in isolated human hair roots. In growing scalp hair roots, the amount of enzyme activity per cell was surprisingly high and was of the same order of magnitude as has been reported for human liver cells and for human fibroblasts cultured in the absence of low density lipoproteins. Hair root enzyme activity showed no diurnal variation, was unaffected by cholestyramine feeding, and was similar in 14 normal subjects, one patient with abetalipoproteinemia, and one homozygote and three heterozygotes with familial hypercholesterolemia. The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in human hair roots appears to be unrelated to the level of low density lipoproteins in the plasma.