Rats were treated daily with high doses of phenobarbital or chlorpromazine for 6 weeks. The animals were sacrificed after 1, 2, 4 and 6 weeks of treatment. At each occasion, plasma levels of ASAT, ALAT, LDH, AP, total T4 and T3, free T4 and T3, and TSH were determined. The thyroids and liver weights were recorded, and the microscopical examination was performed on the liver, thyroids and pituitary gland. The results showed hepatic morphological changes indicative of enzyme induction on weeks 1, 2 and 4. During the first 4 weeks, plasma T4 and T3 were decreased in many individuals and increased in few others, and after 6 weeks of treatment the values for T4 and T3 returned to near normal. An increase in ASAT and ALAT was found at the same occasions. Follicular cell hypertrophy in the thyroids was observed during the first 4 weeks of treatment, in both treated groups, and after 6 weeks the thyroid glands returned to normal, except for a few individuals from the phenobarbital group. The present study has shown that the effect of phenobarbital and chlorpromazine on the thyroid gland function is predominantly due to their effect on the peripheral hormone disposition, as a result of the hepatic microsomal enzyme induction.