Background: Recently a novel topical nail lacquer, ciclopirox solution 8%, has been approved for the treatment of onychomycosis. Objective: This was undertaken to determine the most cost-effective treatment for the treatment of dermatophyte onychomycosis of the toes in the United States in 2000. Methods: The nature of the problem was defined. The drug comparators were ciclopirox nail lacquer, terbinafine, itraconazole (pulse), itraconazole (continuous), fluconazole, and griseofulvin. A decision analytic model that reflected the manner in which pedal tinea unguium is managed was produced. Studies that have evaluated the efficacy of the nail lacquer and the oral antifungal agents for this indication were identified. Appropriate studies were used in a meta-analysis to determine the mycologic and clinical response rates when the drug comparators are used for the treatment for toe dermatophyte onychomycosis. For each drug comparator a cost of regimen analysis was carried out. This is the sum of the drug acquisition cost, the cost of medical management, and the cost of managing adverse effects. Next, the expected cost of management was calculated, disease free days were determined, and a sensitivity analysis was conducted. Results: For each comparator the meta-analytic average mycologic cure (MC) rate and clinical response (CR) rates were: ciclopirox nail lacquer (MC: 52.6 ± 4.2%, CR: 52.4 ± 9.0%), griseofulvin (MC: 41.1 ± 20.4%, CR: 33.7 ± 14.1%), itraconazole (continuous) (MC: 66.3 ± 4.2%, CR: 70.3 ± 4.2%), itraconazole (pulse) (MC: 70.8 ± 5.7%, CR: 73.6 ± 4.6%), terbinafine (MC: 77.2 ± 4.0%, CR: 75.3 ± 2.9%), and fluconazole (MC: 65.6 ± 7.1%, CR: 66.5 ± 11.7%). The cost of regimen for the drug comparators was: ciclopirox nail lacquer $325.2, griseofulvin $1413.1, itraconazole (continuous) $1410.2, itraconazole (pulse) $811.7, terbinafine $890.1, and fluconazole $966.8. The cost/mycologic cure rate and expected cost/expected symptom free day were, ciclopirox nail lacquer ($618.2, 1.69), griseofulvin ($3438.2, 5.3), itraconazole (continuous) ($2126.9, 3.52), itraconazole (pulse) ($1146.4, 2.01), terbinafine ($1153.0, 2.14), and fluconazole ($1473.7, 2.10). The relative cost-effectiveness was ciclopirox nail lacquer 1.00, itraconazole (pulse) 1.19, fluconazole 1.24, terbinafine 1.27, itraconazole (continuous) 2.08, and griseofulvin 3.13. Sensitivity analysis indicated that ciclopirox nail lacquer was a cost effective alternative compared with the oral regimens of terbinafine, itraconazole (continuous), and griseofulvin when clinical response rate was used as the primary efficacy parameter. Conclusion: Ciclopirox nail lacquer solution 8% is a recent addition to the armamentarium of therapies available to the physician and patient for the treatment of onychomycosis. The nail lacquer is a cost effective agent compared with the oral antifungal therapies, terbinafine, itraconazole, fluconazole, and griseofulvin. (J Am Acad Dermatol 2000;43:S81-95.)