The antifungal activity of ketoconazole was studied against fungal pathogens associated with various mycotic infections in animals. A concentration of 10 micrograms of ketoconazole/ml of medium proved fungicidal to Trichophyton verrucosum. The same concentration acted as a strong fungistat against the majority of the tested dermatophytes. Yeasts were generally more sensitive than yeast-like pathogens. Ketoconazole also proved fungicidal against Pityrosporon canis and strongly inhibitory on Cryptococcus neoformans and Torulopsis famata at the lowest used concentration. Candida albicans, Candida tropicalis, and Aspergillus fumigatus required a higher concentration in order for the drug to demonstrate some gross changes. However, variable serious microscopic effects were detected. The most marked effect of ketoconazole was in connection with the dimorphic fungi. The action was fungicidal or strongly inhibitory on both the mycelial form and the tissue phase, respectively. The effect of the drug involved both gross morphologic and microscopic changes of the fungi. The mechanism of action of the drug is described in detail. The results are promising and encouraging for the use of ketoconazole in veterinary medicine.