The study of experimental fungal infections requires effective animal models. Two such models in the rabbit model have been developed and applied to various aspects of topical antifungal therapy. In these models, the polyenes, as a class, are superior in efficacy to the imidazoles and flucytosine, but efficacy is clearly strain related. Corticosteroids, when administered concomitantly with antifungal agents, adversely influence antifungal activity in vivo. This steroid effect is inversely proportional to the efficacy of the antifungal agent. The corneal epithelium appears to be a significant barrier to the penetration of the polyene antibiotics. Although the predictive power of in vitro susceptibility testing as a guide to in vivo efficacy is uncertain, a correlation was seen between the in vivo and in vitro effect for amphotericin B against three strains of Candida albicans.