Because salt stress is a major abiotic source of stress on potato crops, the molecular mechanism of the response of potato plants to salt stress was examined. On exposure to salt, the salt-sensitive cultivar Concord showed a greater reduction in shoot and root length than did the salt-tolerant cultivar Kennebec. For both cultivars, the reduction in the length of shoots was more severe than that of the roots. Salt exposure increased the content of free proline and total soluble sugars in shoots of Kennebec; these remained unchanged in Concord. Proteins extracted from shoots of both cultivars exposed to 90 mM NaCl were separated by two-dimensional polyacrylamide gel electrophoresis: 322 and 305 proteins were detected in shoots of Kennebec and Concord, respectively. Of these, 47 proteins were differentially expressed under NaCl treatment in shoot of both cultivars. Among the differentially expressed proteins, photosynthesis- and protein-synthesis-related proteins were drastically down-regulated, whereas osmotine-like proteins, TSI-1 protein, heat-shock proteins, protein inhibitors, calreticulin, and five novel proteins were markedly up-regulated. These results suggest that up-regulation of defense-associated proteins may confer relative salt tolerance to potato plants.