Compound GZ isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applictions, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of the untreated lesions which healed spontaneously (P < 0.01).Dermatophytes, a closely related group of keratinophilic fungi, cause a wide variety of skin, hair, and nail infections. These fungi have a worldwide distribution and are among the most common infectious agents of humans and animals. They cause both acute inflammatory and chronic noninflammatory types of infection (11). The limited number of available effective antimycotic drugs has stimulated a search for new agents.Compound G2 isolated from alfalfa roots is active in vitro against plant pathogenic fungi (4), medically important yeasts (8, 9), and dermatophytes (2). This compound is the glucp derivative of medicagenic acid, the major saponin aglycon occurrng in alfalfa roots (1). Medicagenic acid, its dimethyl esters, and the malto derivative thereof were also effective against plant pathogenic fungi (46).Compound G2 has a strong affinity for ergosterol, and its fungicidal effect was probably due to increased membrane permeability which caused leakage of ions and small molecules. When sterols were added to the medium, reduced susceptibility of fungi to the drug was observed (M. Levi, I. Polacheck, M. Guizie, U. Zehavi, M. Naim, and R. Evron, submitted for publication).This study describes the topical use of compound G2 for experimental dermatophytosis in the guinea pig, using a model previously shown to simulate human inflammatory fungal infections caused by zoophilic dermatophytes such as Trichophyton mentagrophytes var. granulare and Microsporum canis (11,12, 14). A clinical isolate of T. mentagrophytes var. granulare was used. It was identified by conventional methods (10) and maintained on slants of potato dextrose agar prepared from 20 g of potato infusion (Difco Laboratories), 20 g of dextrose (Difco), and 2.5 g of yeast extract (Difco) containing 50 ,ig of chloramphenicol and 0.5 g of cycloheximide per liter, at pH 5.6. A suspension containing 5 x 107 particles (spores and hyphae) was prepared as previously described (2). Compound G2 was prepared at a concentration of 2.5 mg/ml in a vehicle solution of 0.1% (wt/vol) polyethylene glycol in 2 mM sodium hydroxide, as previously described (9).The backs and flanks of Duncan Hartley female guinea pigs weighing 200 to 300 g were shaven. The exposed skin was lightly abraded with sandpaper to facilitate the adhesion of fungal elements, cleansed with 70%o ethanol, covered with fungal suspension, and occluded. After 3 days, scrapings of * Corresponding author.scales from the infected areas were examined microscopically in 30% KOH and cultured on potato dextrose agar slants. When infection was verified, treatment with compound G2 was started. Compound G2 was applied once daily to the infected le...