Prevalence of, and risk factors for, drug-resistance of Mycobacterium tuberculosis were assessed among 407 hospitalized patients with tuberculosis in Rome, Italy, during the period 1990-1992. Resistance to 1 or more drugs was detected in 106 isolates (26%). Resistance to streptomycin was the most common (18.4%), followed by isoniazid (10.3%) and rifampin (7.9%). 23 isolates (5.7%) were resistant to both isoniazid and rifampin. Resistance to at least 1 drug and resistance to both isoniazid and rifampin were significantly more common among recurrent cases (40.7% vs. 22.1%, p < 0.001; and 22.1% vs. 1.2%, p < 0.001). Sex, country of origin and HIV infection were not significantly associated with prevalence of drug resistance. Among recurrent cases, prevalence of resistance to at least 1 drug and of resistance to both isoniazid and rifampin, was higher in subjects who had had a previous episode of tuberculosis later than 1969. In the population studied the prevalence of drug-resistant tuberculosis was high, although the risk of initially becoming infected with a multidrug-resistant strain of M. tuberculosis in this area appears to be low. This study suggests the need for enhanced surveillance of drug-resistance of tuberculosis in our country and for implementation of intervention aimed to ensure adequate and complete therapy for patients with tuberculosis.