Patients with severe nonthyroidal illnesses (NTIs) frequently have decreased serum concentrations of triiodothyronine (T3) and less often of thyroxine (T4) without clear evidence of hypothyroidism. To determine whether T3 and T4 levels are also reduced in the tissues, we analyzed autopsy samples from 12 patients dying of NTI and 10 previously healthy individuals dying suddenly from trauma. Mean serum T3, T4, and free T4 index values were lower by 79%, 71%, and 49%, respectively, in the NTI group than in controls, but serum thyrotropin (TSH) values did not differ significantly. Mean T3 concentrations in cerebral cortex, hypothalamus, pituitary, liver, kidney, and lung were lower in the NTI group than in controls by 43% to 76%, but mean values in heart and skeletal muscle did not differ significantly between the groups. The mean liver T4 concentration was 66% lower in the NTI group, but mean T4 concentrations in the cerebral cortex were similar in the two groups. These results indicate that many tissues may be deficient in thyroid hormones in patients with fatal NTI, although the severity of the reduction in thyroid hormone concentrations may vary from one organ to another.