Cutaneous lesions caused by Leishmania major in BALB/c mice were cured completely when treated topically with an ointment comprising 15% paromomycin sulphate and 1-2% methylbenzethonium chloride ointment in soft white paraffin twice daily for 10 days. No parasites were detected in tissue smears or in cultures from treated cutaneous lesions. Re-developing lesions, considered to be resulting from the migration of parasites from internal organs, showed almost the same response to topical treatment. Promastigotes of the virulent clone 121 of L. major LRC-L137 which were exposed to 100 μg ml-1 of paromomycin in RPMI medium at 28°C developed resistance to the drug over 10 passages of exposure. Enzyme analysis of susceptible and resistant promastigotes of this clone showed no differences with regard to their profiles based on 11 enzymes.