Minocycline hydrochloride (MCH) is a broad spectrum antibiotic of the tetracycline group that is extensively used to treat skin conditions such as acne and rosacea. Unfortunately, since this antibiotic is highly prone to degradation, no minocyclinecontaining topical product is currently available on the market. In this pilot study, MCH was incorporated into a novel oleaginous foam recently developed by Foamix Pharmaceuticals, Ltd. The product, coded FMX101, was produced in drug concentrations of 1% w/w or 4% w/w. An in vitro porcine skin model was utilized to evaluate the extent of MCH penetration into the skin layers and compartments. The results indicated that topical foam administration allows MCH penetration that is sufficiently deep to treat most typical skin infections, acne and rosacea. Additional studies, using MALDI FTICR imaging and fluorescent microscopy techniques demonstrated visually the residence of MCH in the stratum corneum, the epidermis and the dermis and showed specific targeting to the pilosebaceous unit. The antibiotic foam caused virtually no trans-dermal drug absorption.