About 250 enzyme deficiencies have been demonstrated in the 750 or so recognised human recessive disorders.'Approximately 100 of these enzymopathies can be diagnosed pre-natally. Undoubtedly this number will increase as more methods are developed for the detection of enzymic defects in fetal samples (particularly in chorionic villus samples obtained in the first trimester). There are two main limitations to the application of the enzyme assay procedures used in postnatal diagnosis to fetal samples. Firstly the amount of material available for investigation is very small. Therefore the enzymic assay procedure has to be very sensitive, which may necessitate modification of postnatal methods. Secondly the enzyme under investi-gation may not be expressed in fetal samples that are readily accessible, for example, chorionic villi or cultured amniotic cells, because it is tissue specific. Although sampling of some specialised tissues is possible, the enzymemay still not be expressed at a sufficiently early stage of gestation to allow diagnosis and termination. These problems can, in principle, be overcome by the use of recombinant DNA technology, which detects or tracks mutations in genomic DNA. As this does not require expression of the enzyme protein, it can be applied to any nucleated cell. Currently, however, DNA probes are being used for the prenatal diagnosis of a very small number of enzymic defects (see appendix) and modifications of conventional assay procedures are used predominantly. The expansion of DNA analysis depends upon progress in cloning genes encoding enzymes and in elucidation of the molecular genetical basis of enzymopathies. This article will review the range of enzymic defects that can be detected prenatally and discuss how the method of detection depends upon the molecular basis of the defect, the tissue and subcellular site of action of the enzyme, and the nature of the fetal biopsy available.