Rifampicin produces a dose-dependent decrease in protein synthesis in rat thymocytes. At concentrations up to 200 micrograms per milliliter, rifampicin does not alter rat thymic transcription. Rifampicin causes a direct inhibition of protein synthesis in rat thymic and hepatic microsomes, and in cadaveric human hepatic microsomes. Protein synthesis inhibition could explain the toxicity of rifampicin in man.