Ofloxacin and ciprofloxacin are potentially useful agents for treating mycobacterial infections. We retrospectively reviewed 7 years' experience with these agents in 103 patients. Ofloxacin was used primarily to treat tuberculosis (TB), dosed to achieve 2-hour postdose serum concentrations of 8-12 micrograms/ml. Ciprofloxacin was used primarily to treat Mycobacterium avium complex (MAC) infection, dosed to achieve 2-hour post-dose serum concentrations of 4-6 micrograms/ml. Despite differences in patient characteristics, underlying disease, and concurrent medications, ofloxacin and ciprofloxacin were associated with a similar spectrum and incidence of adverse reactions. Both drugs were generally well tolerated. Adverse effects led to an ofloxacin dosage change in 1 patient (3%) and discontinuation of ofloxacin in 2 patients (6%). Adverse effects led to a ciprofloxacin dosage change in 2 patients (3%) and discontinuation of ciprofloxacin in 5 patients (7%). Ofloxacin and ciprofloxacin appear to be tolerated as well as or better than other "second-line" antimycobacterial drugs.