The clinical effectiveness of rifabutin for prophylaxis of disseminatedMycobacterium aviumcomplex infection has recently been demonstrated in HIV-positive patients with low CD4 counts. Rifabutin is a newly marketed, semisynthetic antimycobacterial agent similar to rifampicin (rifampin) in structure and activity. However, rifabutin has important pharmacokinetic differences compared with rifampicin.Rifabutin has relatively low oral bioavailability; about 20% after single dose administration. With long term administration rifabutin induces its own metabolism and the metabolism of some other drugs. The elimination half-life of rifabutin is long (45 hours) but, as a result of a very large volume of distribution (>9 L/kg), average plasma concentrations remain relatively low after repeated administration of standard doses.In vitrorifabutin is more active againstM. avium-intracellularecomplex and at least as active againstM. tuberculosisas rifampicin.In vivothe advantage of rifabutin is less apparent due to its lower plasma concentrations at equivalent doses. Adverse effects are unusual at the recommended oral dosage of 300 mg/day, but become common as the total daily dose approaches 1g. Dose-limiting toxicity consists of a polyarthralgia/arthritis syndrome, possibly complicated by uveitis. More clinical studies are needed to establish the role of rifabutin in combination therapy forM. avium-intracellularecomplex and other mycobacterial infections.