OBJECTIVE: To provide more data for the discussion on whether thyroid hormones, iodide and other factors controlling the thyroid also influence the parafollicular (PF) cells, as the answer is of great importance for optimization of the medical treatment of medullary thyroid carcinoma (MTC) after surgery. DESIGN: We compared the density of the PF cells in patients who underwent surgery for the second time due to recurrent goiter with that in normal-sized thyroid glands after the first operation. METHODS: In 20 patients with only one operation, all specimens were taken from morphologically and functionally normal lobular thyroid parenchyma. The second group consisted of 30 patients who had already undergone a nearly total resection of at least one thyroid lobe several years before. Then another surgery of the same side was performed due to recurrent goiter. Immunohistochemical staining of the PF cells was performed using primary antibodies to calcitonin and chromogranin. RESULTS: An average of 78 PF cells (median 12.5) was found in the sections with the highest density of the first group. The average number of PF cells in the second group was just 5 (median 0). The Wilcoxon test revealed a highly significant difference in the total PF cell content between the groups (P < 0.001). CONCLUSIONS: Our study suggests that the stimulating factors that lead to growth of the thyroid parenchyma do not influence the PF cells. Hence a non-suppressive thyroid hormone replacement seems to be sufficient after resection of an MTC.