Abstract We have examined the hypothesis that regional differences in 15-hydroxyprostaglandin dehydrogenase (PGDH) activities occur within the human fetal membranes. Further, we reasoned that a specific reduction in PGDH in the fetal membranes at the lower uterine segment might occur with labour, providing a potential mechanism for local generation of primary prostaglandins (PG) that could contribute to cervical ripening. Full-thickness membranes were obtained from patients at caesarean section in the presence or absence of labour. Membranes were sampled from three regions: close to the site of placental attachment, in the region of the internal cervical os, and from a ‘middle’ area between these two. PGDH activities (sum of PGF 2α to 15-keto PGF 2α and 13, 14-dihydro 15-keto PGF 2α conversion) and immunoreactivity varied appreciably between the three regions. PGDH activity was highest in chorion in the cervical region of patients not in labour, but was significantly lower in the chorion from membranes taken closest to the internal os of patients in labour. Loss of PGDH activity was not attributable to a diminution in the number of trophoblast cells in this area. We conclude that regional loss of PGDH in the fetal membranes (chorion) at the lower uterine segment occurs with labour. Reduced PG catabolism could facilitate local generation of bioactive PG at this site for cervical effacement.