Epidermal growth factor (EGF) was first isolated from the mouse submaxillary gland, and later from human urine. The synthesis of mouse EGF is stimulated by thyroid hormone and inhibited by antithyroid therapy. EGF in turn stimulates the growth of thyroid cells. The objective of the present study was to determine whether salivary EGF levels are affected by thyroid hormone level in man. Unstimulated saliva was obtained from 13 (1 male, 12 females) untreated thyrotoxic patients (age 19-64 yr) and from 21 (2 males, 19 females) healthy controls (age 19-68 yr). After centrifugation at 1000 x g, the supernatants were assayed for human (h) EGF in a homologous radioimmunoassay. The mean +/- SEM concentration of hEGF was 0.42 +/- 0.05 nmol/L in controls compared with 0.71 +/- 0.25 nmol/L in thyrotoxic patients (p > 0.05). Thyrotoxic patients with goiter secreted significantly higher concentrations of hEGF (0.92 +/- 0.24 nmol/L) in saliva than did euthyroid controls or nongoitrous thyrotoxic patients (0.31 +/- 0.11 nmol/L, p < 0.01).