A single synthetic T cell epitope (PT3), obtained from the histidine zinc-binding region of the metalloprotease gp63, was employed in a vaccine trial using two virulent strains of L. major. When a single subcutaneous injection of PT3 was delivered with the Thl stimulating adjuvant poloxamer 407, BALB/c mice were protected for at least 10 months against the disease. Vaccinated mice were largely free of lesions on termination of the experiment. Protection was similar for both L. major MRHP/SU/59 Neals and L. major WHOM/IR/-/173 strains which manifest different disease sequelae. Thus, these data provide evidence that a single subcutaneous injection of a single synthetic T cell epitope is sufficient to provide long-lasting protection against two highly virulent strains of L. major in BALB/c mice.