We have employed the recently developed competitive ligand binding assay (CLBA) to study thyroid hormone binding inhibitor (THBI) in ether extracts of sera of 25 patients admitted to the Medical Intensive Care Unit with a variety of nonthyroidal illnesses (NTI). THBI was detected in 60% (15/25) of patients using one sample/patient and in 88% (15/17) using multiple (two to six) samples from different days. Mortality rate and mean serum concentrations of total T4, total T3, and albumin were similar in THBI-positive and THBI-negative patients. There was a tendency for a higher frequency of low serum total T4 in THBI-positive (10/15) than in THBI-negative (3/10) patients but the difference was not statistically significant (P less than 0.1 by Chi square). However, the mean dialyzable fraction of T4 (DFT4 0.11 +/- 0.02%, n = 9 v 0.054 +/- 0.004%, n = 10) and DFT3 (0.54 +/- 0.05% v 0.40 +/- 0.032%) were both significantly (P less than 0.05) higher in THBI-positive patients than THBI-negative patients. There was a significant correlation between THBI and DFT4 (r = 0.55, P less than 0.02) or DFT3 (r = 0.54, P less than 0.02). Prior extraction of serum with ether reduced DFT4 in NTI patients with high baseline DFT4 but not in normal subjects or NTI patients with mildly abnormal baseline DFT4. Addition to a normal serum (0.1 mL) of evaporated ether extract of a pooled NTI serum (0.10- to 3.0-mL equivalent) increased DFT4 progressively from 0.025% to 0.14%. Similar extract of a pooled serum of normal subjects had little or no effect.(ABSTRACT TRUNCATED AT 250 WORDS)