Magnesium (Mg) and zinc (Zn) status was assessed in subjects to evaluate the effects of thyroid diseases on Mg and Zn metabolism. Plasma and red blood cell (RBC) concentration and peripheral blood mononuclear cell (MNC) content of Mg and Zn, and 24-hour urinary excretion of Mg, Zn, creatinine (Cr), calcium (Ca), sodium (Na), and potassium (K) were measured in 11 thyrotoxic, 29 hypothyroid, and 25 euthyroid control subjects. Serum albumin, alpha 2-macroglobulin, and the binding of Zn to albumin were also determined. Plasma and RBC Mg concentrations were low in half of the hyperthyroid subjects, but mean values were not significantly different from controls. Urinary excretion and clearance of Mg were lower in hypothyroid subjects, but differences were removed when expressed relative to Cr excretion and clearance. Similar patterns were noted for urinary Ca, Na, and K, suggesting that their reduced excretion reflects alterations in renal hemodynamics. Plasma Zn was lower in hypothyroid subjects and correlated with serum albumin; MNC Zn and urinary Zn were also low. Plasma Zn concentration was normal and serum albumin significantly lower in the hyperthyroid group than in the control group. Further, RBC Zn content was significantly lower in hyperthyroid subjects, and inversely related to plasma thyroxine concentration. The hyperthyroid group also excreted significantly greater amounts of Zn than controls, indicative of a catabolic process. This increased urinary loss may reflect a shift in the distribution of plasma Zn between ultrafilterable and Zn-albumin complexes. In summary, this study provides evidence for marked alterations in Zn homeostasis in persons with thyroid disease. Whether the observations indicate deficiency states and have clinical implications will require further investigation.