Seventy-two patients with gestational trophoblastic tumors (GTTs) and 20 first-trimester healthy pregnant women (controls) participated in this study. According to the WHO scoring system, GTTs were subgrouped into 24 hydatiform mole spontaneous regression (HMSR), 18 postmolar high-risk (PMHR) and 16 low- and 14 high-risk cases of choriocarcinoma. Patients with choriocarcinoma were treated with hysterectomy and methotrexate chemotherapy, whereas molar pregnancy was managed by either oxytocin infusion followed by suction evacuation or by hysterectomy. Serum p53 autoantibodies were determined by enzyme-linked immunosorbant assay and serum hCGbeta was determined by radioimmunoassay before and throughout the 12 months after treatment. p53 autoantibodies were not detected in normal pregnancy and cases of HMSR but were detected in all cases of PMHR and choriocarcinoma. Concentrations of p53 autoantibodies were higher in choriocarcinoma than in PMHR cases. Serial measurements of p53 autoantibodies dropped to an undetectable level within 1 and 6 months after treatment in cases of PMHR and low-risk choriocarcinoma, respectively. Decreasing values of p53 autoantibodies in high-risk choriocarcinoma remained higher than the cut-off level of controls. There was a significant positive correlation between p53 autoantibodies and serum hCGbeta concentration in GTTs. In conclusion, detection of p53 autoantibodies has a high potential for the differential diagnosis of GTTs and their serial measurements are clinically useful to monitor disease progression and to assess response to therapy in GTTs.