1. Drug-resistant tuberculosis is a growing health care problem. When a series of cases occur, it is essential to know if patients with multidrug-resistant disease represent one or a number of separate outbreaks. 2. The epidemiology of an outbreak of isoniazid- and streptomycin-resistant tuberculosis in Blackburn was studied by restriction fragment length polymorphism using a probe for the IS6110 DNA sequence. 3. Mycobacterium tuberculosis from four cases of isoniazid- and streptomycin-resistant disease had an identical restriction fragment length polymorphism pattern. This pattern was not shared by drug-sensitive isolates of M. tuberculosis obtained from Blackburn (n = 8) or London (n = 13) or a M. tuberculosis isolate from a fifth Blackburn case which was resistant to isoniazid alone. 4. This methodology confirmed that all four cases of isoniazid- and streptomycin-resistant disease were part of a single epidemiologically related outbreak of drug-resistant disease. This study demonstrates how the epidemiology of an outbreak of multidrug-resistant tuberculosis in the U.K. can be confirmed by restriction fragment length polymorphism.