Topical metronidazole is effective in the treatment of papulo-pustular rosacea, a common inflammatory disease of the face. In this study, a comparison of the bio-availability of two topical formulations (A and B) of 0.75% metronidazole has been made. Twenty-four subjects took part in a double-blind study where each was randomly allocated to four groups corresponding to 0.5, 1, 2 and 4 h of treatment. A single application was made to each forearm and after increasing times of contact, samples of stratum corneum were removed by the skin surface biopsy (SSB) technique. After SBB removal, a full-thickness skin biopsy was taken. The tissues were extracted and analysed by an HPLC method. Both formulations showed rapid percutaneous penetration. Formulation A gave the highest concentrations at the lowest levels of the stratum corneum at 4 h. Thus in SSB5, the mean drug concentrations at 4 h were as follows: A, 6.20 ± 1.16 μg cm-2; B, 1.93 ± 0.98 μg cm-2. A similar difference was observed when the levels in the punch biopsies were determined. At 4 h, the mean drug levels were: A, 6.07 ± 2.17 μgmg-1; B, 0.95 ± 1.16 μgmg-1. Formulation A clearly gives a higher rate of percutaneous penetration leading to higher tissue levels of drug. Whether this increase leads to a clinically more effective treatment has yet to be det