Previous recommendations for the use of thyroid function tests to diagnose patients with possible hypothyroidism have discounted the value of a total thyroxine (T4) test because many clinically hypothyroid patients have T4 levels that fall within the "normal" range. The authors examined the predictive value of a total T4 measurement in the evaluation of ambulatory general medical patients suspected of having hypothyroidism. Pregnant patients and those who were taking medications that interfere with thyroid homeostasis were excluded. Simultaneous T4 and thyrotropin (TSH) tests of 93 consecutive outpatients suspected to have hypothyroidism but found to be euthyroid and 27 patients discovered to be hypothyroid (TSH greater than 10 microU/ml) were examined. A T4 of 7.0 microliter/dl or less had a sensitivity of 93% with a false-positive rate of 19%. A T4 greater than 8.0 microgram/dl appeared to exclude hypothyroidism (negative posttest probability of 100%). It may be possible to achieve cost savings without loss of diagnostic accuracy by using a single total T4 measurement for the initial evaluation of suspected hypothyroidism in selected outpatients.