Background: Therapeutic limitations of griseofulvin in treating onychomycosis have led to a search for alternative antimycotic agents. An optimal dosing regimen for fluconazole has yet to be defined. Objective: Our purpose was to evaluate the intermittent use of fluconazole (either once-weekly or alternate-day dosing) without concurrent nail avulsion in patients with moderate to severe onychomycosis. Methods: Eleven patients with mycologically confirmed onychomycosis of the toenails or fingernails (43 infected nails) were treated with intermittent fluconazole until clinical cure was obtained. Eight patients received fluconazole 300 mg once weekly, one patient received 200 mg once weekly, and two patients received 100 or 200 mg of fluconazole every other day. Eight patients also used an adjunctive topical antimycotic preparation. Results: All six patients with toenails involved (32 infected nails) were clinically cured after a mean treatment duration of 6 months, and all five patients with fingernails involved (11 infected nails) were cured after 3.7 months. There were no significant clinical or laboratory adverse events. Conclusion: Intermittent fluconazole, taken once weekly or on alternate days, is a well-tolerated and efficacious method to treat onychomycosis. Copyright © 1996 by the American Academy of Dermatology, Inc.