Introduction: This study was performed to establish a complementary method to the diagnosis of complete hydatidiform mole and its differentiation from the other cases of gestational trophoblastic disease by measuring the total (ALP) and placental alkaline phosphatase (PLAP) specific activity. Materials and Methods: Serum and tissue extracts from 13 patients, 13 normal non-pregnant and 30 pregnant females were compared for these enzymes activities. Paranitrophenyl phosphate was used as substrate. Placental alkaline phosphatase was simply distingushed from its isoenzymes by its heat stability (65°c for 15min). Results: According to our findings from serum and tissue extract examination the activity of total alkaline phosphatase and placental alkaline phosphatase activities were reduced in hydatidiform mole patients in comparsion with pregnant females (P<0.05) but there was no significant difference in non - pregnant subject. Conclusion: These results show a severe hypophosphatasia in serum and tissue extracts of the patients. The reduction in activity of enzymes may be caused by low synthesis of enzyme by trophoblast cells or some post transcriptional changes that causse the reduction of enzyme activity. Since the ALP is probably important in active transport of suger and phosphate across the trophoblast cell membreanes, so the hy<font>drop</font>ic villi of hydatidiform mole placenta may due to reduction of enzyme activity in placental villi. Our results suggest that measurment of ALP and PLAP activity in serum and tissue extract can be a complementary method in diagnosis of hydatidiform mole.