Background: Superficial basal cell carcinoma (sBCC) is an increasingly common tumor in fair-skinned populations throughout the world. Imiquimod, an immune response modifier that induces cytokines including interferons, has been shown in preliminary studies to have an effect when applied topically to BCC. Objective: We conducted a multicenter, randomized, open-label dose-response trial of imiquimod 5% cream in the treatment of primary sBCC assessing efficacy and safety of different dose regimens. Methods: Ninety-nine patients were randomized to 6 weeks' application of imiquimod in 1 of 4 treatment regimens: twice every day, once every day, twice daily 3 times/week, once daily 3 times/week. The treatment site was excised and examined histologically 6 weeks after cessation of imiquimod. Results: Intention-to-treat analysis revealed 100% (3/3) histologic clearance in the twice-daily regimen, 87.9% (29/33) clearance in the once every day regimen, 73.3% (22/30) clearance in the twice-daily 3 times/week regimen, and 69.7% (23/33) clearance in the once-daily 3 times/week regimen. Dose-related inflammatory skin reactions at the site of application were common. The majority were well tolerated and only 1 patient withdrew from the trial as a result of a medication-related skin reaction. Conclusion: Imiquimod 5% cream appears to have potential as a patient-administered treatment option in sBCC. (J Am Acad Dermatol 2001;44:807-13.)