The acute (within hours) changes in the concentrations of T₄, T₃, reverse-T₃ (rT₃) and T₃ resin uptake test (T₃RU) were studied in 31 hyperthyroid patients for 4 h after po treatment with either acebutolol, Oxprenolol, pindolol or timolol. In 21 of the patients, the changes were compared to changes in the serum concentrations of α₂-macroglobulin (a macromoleculë) and two middle-sized molecules; thyroid hormone-binding globulin (TBG) and albumin in order to calculate the changes in extracellular distribution of the thyroid hormones and to distinguish between changes due to a changed metabolism and changes due to a changed distribution of the thyroid hormones. Acebutolol, Oxprenolol and timolol caused a decrease in serum T₃ after 1/2 h, and acebutolol and Oxprenolol also a decrease in rT₃ after 1/2-1 h, the changes reversed within 2 h. A concomitant decrease in serum albumin and TBG suggests a change in the extracellular distribution of middlesized molecules to which thyroid hormones are attached, as an explanation of the acute decrease (1 h) of the thyroid hormones. The small and insignificant change in α₂-macroglobulin indicates that the changes are mainly extravascular, but the difference of α₂-macroglobulin changes between the drugs (acebutolol/timolol vs pindolol/oxprenolol) could depend on the intrinsic sympathomimetic activity of the drugs.