A newly developed method for extracting and measuring methimazole in biological fluids was used to study the pharmacokinetics of methimazole in two euthyroid and eight hyperthyroid subjects. The volume of distribution approximated total body water; the biological half-life was 2-3 h in euthyroid and about 6 h in hyperthyroid patients. Total clearance was lower in hyperthyroid patients than in euthyroid subjects, and it did not increase after thyroid function was normalized. Bioavailability in euthyroid subjects was greater than 1 but only 0.5 in hyperthyroid subjects. The reasons for these observed differences are not known.