Three new types of regulatory somatic cell mutants defective in expression of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase are described. They include a recessive mutant with abnormally high enzyme activity, apparently defective in degradation of the enzyme, and one, phenotypically a mevalonate auxotroph, that maintains permanently repressed levels of enzyme activity and are recessive, constitutive mutants. These mutants offer means for analyses of the mechanism of regulation of expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase in cultured fibroblasts.