Intranasal instillation of an inoculum has been suggested as a method for establishment of experimental pulmonary infections. Because we encountered untoward variation in rates and times of death with use of this method for inducing coccidioidomycosis in mice, a simple method for direct intratracheal infection was devised. With doses of 50 or 100 arthrospores of Coccidioides immitis, mortality rates were 80%-90% from 14 to 25 days after infection by the intratracheal route and 20%-60% from 12 to 24 days after infection by the intranasal route. The procedure for intratracheal infection caused only slight morbidity, and the method resulted in consistent rates of disease.