Between 1977 and 1990 we operated on 33 patients with medullary thyroid carcinoma. We performed total thyroidectomy in 31 patients and central node dissection and/or lateral modified node dissection in 21 patients (63.3%). Two patients underwent radiotherapy after subtotal resection and tracheostomy. No perioperative death occurred. Twenty-five patients were followed (mean follow-up, 63.8 months) and 8 others were unavailable for follow-up. Three patients (1 with multiple endocrine neoplasia type IIB, 2 sporadic with distant metastases) died of their disease at 12, 18 and 36 months after initial operation. Of the remaining 22 patients, 4 with stage II disease were normocalcitoninemic even with pentagastrin stimulation, following total thyroidectomy and bilateral modified neck dissection and central node dissection. Eighteen other patients continued to have elevated calcitonin levels postoperatively. Only 10 patients with known cervical metastatic disease were reoperated upon. We performed extensive node dissection in all. In addition we resected recurrent tumor from the thyroid bed in 4 patients. Despite these extensive reoperations no patient became normocalcitoninemic. At the completion of the study (December 1991), 22 of the 25 patients followed were alive: 4 patients with normal calcitonin levels, baseline and after pentagastrin stimulation, and 18 with persistent mildly elevated calcitonin levels but no other evidence of disease. Our experience supports a very aggressive surgical approach at the time of the first operation for patients with medullary thyroid carcinoma. A lesser operation usually resulted in residual medullary thyroid carcinoma in the neck. We demonstrate the difficulty of achieving a cure by reoperation once the tumor becomes demonstrable by localization studies.