Oral administration of ambruticin (W7783) (by gavage) was lifesaving in mice infected intranasally with arthrospores of Coccidioides immitis. Doses of 25 and 50 mg/kg of body weight, given twice daily by different schedules for from 17 to 60 days, eradicated the fungus from 71 to 100% of the infected mice. Lower doses (5 or 10 mg/kg once or twice daily by an intermittent 50-day regimen) prevented death in all instances but produced many fewer biologic cures. The animals tolerated all these doses well but were adversely affected by doses of 200 mg/kg given daily. Resistance to the drug was not induced by prolonged treatment. Dose-related fungicidal and fungistatic properties in vitro correlated with doses that were life-sustaining or curative (or both) in vivo.