Serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) were evaluated in a group of 41 patients with histologically proven medullary thyroid carcinoma (MCT) before and sequentially after treatment for a period up to 7 years. Before thyroidectomy, CT levels were high in all patients, and significantly more elevated when metastases were present. On the other hand, CEA levels were high in most but not all the patients, and they also were found more frequently to be elevated in patients with metastases. After treatment, most of the patients without metastases showed persistently normal basal and pentagastrin stimulated CT and CEA levels. In some patients either without or with local metastases, postoperative CT levels, although considerably reduced, remained persistently above normal limits, whereas CEA levels became completely normal. This pattern may be due to the persistence of minute occult foci of the tumor, not sufficient to produce measurable amounts of CEA, which is not synthesized by all tumor cells. Most of the patients with metastases at diagnosis, showed still elevated CT and CEA levels after treatment. In the nonprogressive cases both markers decreased after adjunctive treatment or remained unchanged. In patients with progressive disease, an increase of CEA levels in the absence of a parallel increase of CT levels, which even decreased, was often observed. In one patient with progressive disease high CEA levels were seen for the first time when liver metastases had occurred. These data seem to suggest that, even though CEA production is not recognizable in all patients with MCT, in the CEA positive cases CEA levels may follow a nonparallel pattern and may have a distinct diagnostic meaning with respect to CT levels. In some cases, particularly in advanced disease, CEA may be a more useful marker of poor prognosis.