A drug-induced stimulation of heme biosynthesis in mouse liver was accompanied by altered fumarate metabolism. In liver homogenate, fumarate 1,4-C14 was incorporated, via succinate and succinyl coenzyme A, into heme at an accelerated rate. This pathway of fumarate utilization was inhibited by acetoacetate but not by β-hydroxybutyrate. Fumarate reduction to succinate required reduced nicotinamide adenine dinucleotide. The enzyme fumarate reductase is suggested as a link between terminal oxidation and cellular control of the heme biosynthetic pathway.