1 The effect of different combinations of liver microsomal enzyme inducing drugs on thyroidal hormone steady state concentrations was investigated. Three groups of healthy volunteers were given daily either antipyrine 1200 mg together with phenobarbitone 100 mg, antipyrine 1200 mg combined with rifampicin 600 mg or rifampicin 600 mg alone for a period of 14 days. 2 Before and after each treatment the total body clearance of antipyrine, gamma-glutamyl transferase (gamma-GT), 6 beta-OH-cortisol as in vivo parameters of liver microsomal enzyme activity were measured. In addition, thyroxine (T4), free thyroxine (FT4), T3 resin uptake, tri-iodothyronine (T3) reverse T3 (rT3) and TSH were estimated. 3 After rifampicin administration there was a 60% increase in antipyrine clearance while following combinations of antipyrine-phenobarbitone or antipyrine-rifampicin an 80% and 128% increase respectively occurred. 4 A marked decrease of T4, FT4 and rT3 was seen in all groups while T3 remained stable in all groups investigated. This effect may be partly due to an increase in extrathyroidal metabolism of T4 as found previously by a kinetic turnover study using 125I-T4. It also depends on the extent of the liver microsomal enzyme inducing capacity rather than on the nature of the drugs used. The striking disparity of liver enzyme induction of T4 and rT3 disposal on the one hand and T3 metabolism on the other is a unique phenomenon whose pathogenesis is not clear at the present time.