To determine the effects of neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma Stage IB2 (tumor diameter > 4 cm), we reviewed 52 surgically treated patients diagnosed between January 1987 and December 1993. There were 20 patients treated with preoperative neoadjuvant chemotherapy and 32 treated by primary radical hysterectomy. Mean tumor diameter was significantly larger in the neoadjuvant, compared with the primary surgery group (6.5 +/- 1.8 vs 5.4 +/- 0.7, P = 0.003). In the NAC group, 5 of 20 patients were treated with three courses of cisplatin, methotrexate, and bleomycin every 21 days, whereas 15 of 20 patients received three courses of cisplatin, vincristine, and bleomycin every 10 days. Postoperative adjuvant therapy consisting of either radiation or chemotherapy was employed in 13/20 patients (65%) in the NAC group and 20/32 patients (63%) in the primary surgical group. At a median follow-up of 52.5 months, 4/20 patients (20%) in the NAC group recurred vs 11/32 (34%) in the primary surgery group. The overall response rate to NAC was 90%, with 2/20 complete clinical responders and 16/20 partial responders. High-risk pathologic factors were less commonly observed in the NAC group when compared with the primary surgical group with the incidence of nodal metastases, positive vascular space involvement, undiagnosed parametrial disease, and > or = 75% depth of invasion observed in 10.0% vs 37.5%, 20.0% vs 46.9%, 0.0% vs 15.6%, and 30.0% vs 68.8%, respectively. No differences were noted in operative time or blood loss. Cox proportional-hazards analysis indicated that the most significant prognostic factor was depth of invasion. Although the patients who received neoadjuvant chemotherapy had significantly larger tumors at baseline, their 5-year survival rate was slightly higher than that of the primary surgery group (80.0% vs 68.7%, P = 0.162). Patients receiving neoadjuvant chemotherapy, despite having significantly larger pretreatment tumors, had fewer high-risk pathologic factors, postoperatively. Although this was a small, nonrandomized study, the relative improvement in pathologic response and long-term outcome associated with neoadjuvant chemotherapy was encouraging. This highlights the need for a prospective randomized clinical trial to establish whether neoadjuvant chemotherapy can significantly improve the long-term outcome of women with Stage IB2 squamous cell carcinoma of the cervix.