Syrian hamsters were infected with Sporothrix schenckii by subcutaneous footpad inoculation. Two types of infection could be uniformly induced: a self-limited, lymphatic infection resembling the classical disease in humans, and a generalized nonfatal infection. An infecting dose of approximately 5,300 yeast cells produced the localized subcutaneous-lymphatic disease which was limited to a single limb. In contrast, a 1,000-fold increase in the inoculum temporarily overwhelmed the animals' defense mechanisms, producing a systemic infection involving the liver and spleen. These models were used to demonstrate the development of increased resistance to subsequent infection following either infection or active immunization with ribosomal fractions or trypsinized cell wall antigens of S. schenckii incorporated in Freund complete adjuvant. Agglutination titers were detectable in all animals that were either infected or immunized. In one group of infected animals, the titers persisted for at least 1 year after three booster doses of Formalin-killed S. schenckii. The ability to produce an infection in hamsters which closely resembles the disease seen in humans makes the animal a good model with which to study experimental sporotrichosis.