Seven of the nine vulture species in South Africa are listed as endangered on the International Union for the Conservation of Nature (IUCN) red list. From these, the Cape Griffon vulture (Gyps corprotheres) is the most endangered species in the region. Although inadequate nutritional support has been blamed on the constant decline in populations, the process of vulture restaurants has failed to improve the population status over the last twenty years. One possible reason for the decline may be an underlying reproductive disorder as described in endocrine disruptive syndromes. Both DDT and p,p'-DDE have been detected previously at very high concentrations in the mid 1980s, with lower concentrations still being detectable as late as 2001. To establish the effect of DDT and DDE, the vulture estrogen receptor alpha (ERalpha) was sequenced from two species using 5' and 3' rapid amplification cDNA ends (RACE). Using transient transfected mammalian cell assays, vulture ERalpha estrogen-dependent transcription activity was validated using various estrogens and DDT derivatives. The receptor assay was sensitive to p,p'-DDT, o,p'-DDT and p,p'-DDE with EC(50) of 2.41x10(-6), 3.47x10(-7) and 3.81x10(-5)M. When compared to results obtained from human, zebrafish, chicken, salamander and turtle, the vulture ERalpha showed high sensitivity to o,p'-DDT and intermediately responsive to p,p'-DDE. Vulture ERalpha is, however, not responsive to the DDT and DDE levels reported in the plasma of vultures from the last population survey, indicating that the Southern African vulture are not currently exposed to disruptive levels of these contaminants.