In order to compare the effect of 3,5,3 0 -triiodothyroacetic acid (TRIAC) with those of triiodothyronine (T 3 ) and thyroxine (T 4 ), severely hypothyroid rats (n ¼ 56) were infused over 13 days with 1, 2 or 4 nmol/100 g body weight (BW) per day of T 3 or 2, 4 or 8 nmol/100 g BW per day of T 4 or TRIAC. The 8 nmol/100 g BW per day of T 4 or TRIAC induced the same increase in resting metabolic rate, yet 4 nmol/100 g BW per day of T 3 was more potent (P < 0.05). For inhibiting serum TSH levels, 2 nmol/100 g BW per day of TRIAC were significantly less active than 2 nmol/100 g BW per day of T 4 or 1 nmol/100 g BW per day of T 3 (TRIAC, serum TSH 35.5 Ϯ 5.7; T 3 2.58 Ϯ0.91; T 4 2.12 Ϯ0 .59 ng/ml). At higher doses serum TSH and b-TSH mRNA were unmeasurable.Using serum T 3 levels as covariate, the action of T 3 and T 4 was identical on cardiac monodeiodinase type 1 (5 0 D1) activity and hepatic malic enzyme (Me) mRNA levels and similar for hepatic 5 0 D1 activity. The effect of TRIAC was compared with T 3 by using increasing doses of 1, 2 and 4 nmol/100 g BW per day of T 3 and 2, 4 and 8 nmol/100 g BW per day of TRIAC. ANOVA indicated that there was no major difference between the effects of the hormones since with increasing doses the response of hepatic 5 0 D1 mRNA levels and enzyme activity and Me mRNA remained parallel. However, when studying the effect on cardiac 5 0 D1 activity there was not only a difference for type of treatment (T 3 >TRIAC) but this difference became greater with each increment in dose. Interestingly there was also only a small effect of TRIAC on increase in heart weight compared with T 3 and T 4 . Brain cortex monodeiodinase type 2 (5 0 D2) was mainly inhibited by T 4 infusions. Monodeiodinase type 3 (5 0 D3) was stimulated by T 4 , less so by TRIAC and least by T 3 , expressing probably the local T 3 and TRIAC concentrations.In conclusion, despite apparently similar effects of TRIAC and T 3 and T 4 on hepatic parameters of thyroid hormone action, TRIAC differs considerably in terms of its effects on cardiac 5 0 D1 activity and possibly on other fundamental effects of thyroid hormones on the heart since heart weight increased significantly less with TRIAC than with T 3 or T 4 .