In order to clarify the role of free fatty acid (FFA) in thyroid hormone abnormalities in patients with nonthyroidal illness, thyroid function, FFA, inhibitor of extrathyroidal conversion of T₄ to T₃ (IEC) and thyroid hormone binding inhibitor (THBI) were studied in 99 patients with various nonthyroidal illnesses including diabetes mellitus (DM)(n=35), liver cirrhosis (LC)(n=33), chronic obstructive pulmonary disease (COPD)(n=17) and chronic heart failure (CHF)(n=14). Patients were divided into three groups based on the level of serum T₃: Group I (T₃<50ng/dl), Group II (50≤T₃<80) and Group III (80≤T₃). Serum T₄, FT₃ and the T₃/T₄ ratio decreased significantly in the order Group III, Group II and Group I (Group III>II>I). The plasma FFA level was 0.91±0.12mmol/l in Group I (P<0.05, vs. Group III), 0.65±0.06 in Group II and 0.54±0.04 in Group III, respectively. The incidence of positive IEC was 80.0% in Group I (P<0.05, vs. Group III), 53.7% in Group II (P<0.05, vs. Group III) and 34.2% in Group III. However, IEC was not correlated with the serum T₃ concentration. The incidence of positive THBI was 80% in Group I (P<0.05, vs. Group III), 68.3% in Group II and 47.4% in Group III, but THBI was not correlated with the serum T₄ level. Positive correlations were observed among FFA, IEC and THBI (P<0.001). From the standpoint of the underlying illnesses, DM and LC patients with low T₃ had higher plasma FFA and higher incidence of positive IEC and THBI than those with normal T₃. In patients with COPD, plasma FFA was not increased and the incidence of positive IEC and THBI was low regardless of their T₃ levels. Patients with CHF had high plasma FFA and a high incidence of positive IEC and THBI regardless of their T₃ levels. These results suggest that FFA might act as both IEC and THBI, but the degree of the contribution of IEC and THBI to the thyroid hormone abnormalities might differ according to the type underlying illness.