The standard treatment for tinea capitis caused by Microsporum species for many years has been oral griseofulvin, which is no longer universally marketed. Voriconazole has been demonstrated to inhibit growth of Microsporum canis in vitro. We evaluated the efficacy and tissue pharmacokinetics of oral voriconazole in a guinea pig model of dermatophytosis. Guinea pigs (n ؍ 16) were inoculated with M. canis conidia on razed skin. Voriconazole was dosed orally at 20 mg/kg/day for 12 days (days 3 to 14). The guinea pigs were scored clinically (redness and lesion severity) and mycologically (microscopy and culture) until day 17. Voriconazole concentrations were measured day 14 in blood, skin biopsy specimens, and interstitial fluid obtained by microdialysis in selected animals. Clinically, the voriconazole-treated animals had significantly less redness and lower lesion scores than untreated animals from days 7 and 10, respectively (P < 0.05). Skin scrapings from seven of eight animals in the voriconazole-treated group were microscopy and culture negative in contrast to zero of eight animals from the untreated group at day 14. The colony counts per specimen were significantly higher in samples from untreated animals (mean colony count of 28) than in the voriconazole-treated animals (<1 in the voriconazole group [P < 0.0001]). The voriconazole concentration in microdialysate (unbound) ranged from 0.9 to 2.0 g/ml and in the skin biopsy specimens total from 9.1 to 35.9 g/g. In conclusion, orally administered voriconazole leads to skin concentrations greater than the necessary MICs for Microsporum and was shown to be highly efficacious in an animal model of dermatophytosis. Voriconazole may be a future alternative for treatment of tinea capitis in humans.Dermatophytes are keratinophilic fungi that infect tissue containing keratin such as hair, nails, and skin. Dermatophytes consist of three genera: Microsporum, Trichophyton, and Epidermophyton. Microsporum species, with Microsporum canis predominating, are frequent causes of scalp ringworm, tinea capitis, in Europe (9). M. canis is zoophilic and can be transmitted to humans during close contact with an infected animal, mainly cats and, to a lesser extent, dogs. Other Microsporum species, e.g., M. audouinii and its variants M. langeronii and M. rivalieri, are anthropophilic, and infections are transmitted between humans, sometimes causing epidemics (9). Tinea capitis primarily affects children (3).Oral griseofulvin has long been the standard treatment of tinea capitis; however, this agent has been withdrawn from the market in several countries in Europe. Alternative antifungal agents have been suggested: itraconazole, which is not universally licensed for the treatment of children (7, 10); fluconazole, which in most comparative studies appears to be less effective when M. canis is involved and which is not approved for tinea capitis in the United States (8); and finally terbinafine, which again is less efficient in Microsporum than in Trichophyton infections (6). Although ...