Tioconazole (UK-20,349), a new antifungal imidazole derivative, was compared with miconazole for activity in vitro against Candida spp., Torulopsis glabrata, Cryptococcus neoformans, Aspergillus spp., and dermatophyte fungi (Trichophyton spp. and Microsporum spp.). Tioconazole was more active than miconazole against all the fungal species examined except Aspergillus, against which both agents showed similar activity. Both tioconazole and miconazole inhibited the growth of all fungi examined at concentrations well below their quoted minimum inhibitory concentrations. Their activity against fungi in vivo was investigated in mice infected systemically with Candida albicans. Both agents significantly reduced the numbers of viable Candida cells recoverable from the kidneys of infected animals, with tioconazole producing a generally more marked reduction. After administration of a single oral dose (25 mg/kg) to beagle dogs or white mice, higher and more sustained circulating levels of bioactive drug were detectable of tioconazole than of miconazole. These observations suggest that tioconazole may have potential in the treatment of both superficial and systemic mycoses in humans.