A Cellogel procedure for electrophoretic characterization of formaldehyde dehydrogenase (FDH) is described. Isozyme profiles in 24 different human tissues indicate extreme quantitative heterogeneity and the existence of one major form and at least two minor forms of FDH in man. Biochemical and genetic analysis of the enzyme in Chinese hamster-human somatic cell hybrids has shown that the functional molecule of FDH is probably composed of two identical subunits and that its structural locus may be assigned to human chromosome 4.