OBJECTIVE--To examine the extra cost of using higher-priced drugs as initial therapy for dermatophyte infections, because the many available effective drugs vary considerably in cost. DESIGN--Cost analysis from the purchaser's perspective, comparing two prototypical regimens to treat tinea pedis: one in which all patients initially receive a lower-priced drug and those with unresponsive infections receive a higher-priced drug at a follow-up office visit, and one in which all patients receive the higher-priced drug from the outset. The reference drug was miconazole, an imidazole available without a prescription, for which reported overall efficacy rates are 70% to 100%. MAIN OUTCOME MEASURES--The threshold efficacy rate (the efficacy rate of miconazole below which it is always less expensive to use a specific higher-priced drug first) and the extra cost (of beginning therapy with a higher-priced drug). RESULTS--Assuming the Medicare-approved charge for a follow-up visit ($21.98), it is less expensive to begin therapy with a prescription drug only if the efficacy rate of miconazole is less than 55%; this threshold efficacy rate varied from 26% (for a $0 total cost of the follow-up visit) to 79% (for an $89 total cost of the follow-up visit). If the efficacy rate of miconazole is 70%, the extra cost per patient for all patients to receive the least expensive prescription antifungal drug instead of miconazole first was $15.23 and $8.64 if total visit costs were $0 and $21.98; miconazole remained the less expensive alternative as long as the total cost of the follow-up visit was less than $50.76. CONCLUSION--For reported efficacy rates and standard costs of a follow-up office visit, using miconazole first and then treating only those patients with unresponsive infections with a higher-priced prescription drug is less expensive than treating all patients with the higher-priced drug.