Recent in vitro susceptibility studies have shown that amikacin inhibits more than 90% of isolates of Nocardia. This study was designed to evaluate the effect of treatment with amikacin or sulfonamides on infection caused by Nocardia asteroides with the use of murine models. In an acute lethality model in which infection was induced by intraperitoneal injection, 13 (45%) of 29 mice that had been treated with amikacin survived, in comparison to zero of 39 untreated animals in the control group and one of 39 mice that had been treated with sulfadiazine (P less than 0.001 for amikacin). When infected with a strain of N. asteroides that was resistant to amikacin, all mice that were treated with amikacin and all untreated mice died. Drug therapy was also evaluated in a chronic infection model, in which abscesses were produced by an intraperitoneal injection of N. asteroides in saline. Treatment with either amikacin (P less than 0.001) or sulfonamide (P less than 0.02) for two to three weeks significantly increased the rate of resolution of these abscesses. These murine models demonstrate that amikacin has in vivo activity against Nocardia and may be potentially useful in the treatment of human disease.