No additive effect was found at the addition of isoniazid to either dapsone or protionamide against M. leprae and against highly dapsone-sensitive in vitro growing Mycobacterium sp. strains. It is concluded that the indication of the administration of isoniazid in leprosy is extremely limited and could only be envisaged as a companion drug in combined therapy of dapsone-resistant multibacillary leprosy in light-skinned people, when aminoglycosides cannot be administered.