Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the hepatic alanine:glyoxylate aminotransferase enzyme encoded by the AGXT gene on chromosome 2. Prenatal diagnosis of PH1 either by measurement of hepatic enzyme activity or DNA analysis provides a valuable contribution to the management of pregnancies at risk for the severe infantile form of this disease. DNA analysis is preferred because it can be performed earlier in pregnancy and eliminates difficulties encountered in measurement of tissue enzyme activity, particularly those related to sample instability. We have assessed the clinical value of two polymorphisms located in introns 1 and 4 of the AGXT gene as linkage markers for the prenatal diagnosis of PH1 in 12 families. Eight of the twelve families were informative when either one or a combination of the two polymorphisms was used and prenatal diagnosis has been performed in two of these. The remaining four families were only partially informative. Five additional linkage markers on chromosome 2 have been identified which are co-inherited with the AGXT gene. Assays to detect these markers are currently under development.