Chenopodiaceae pollens such as those from Salsola kali and Chenopodium album are important causes of allergy in Mediterranean areas because of the progress of desertification in European countries. Among the different allergenic protein families, profilins constitute a group of panallergens involved in polysensitization and pollen-food allergy syndrome. Two-dimensional electrophoresis analysis of S. kali profilin highlights a polymorphic pattern with several isoforms showing different molecular (isoelectric point and molecular mass) and immunological features. Two isoforms have been cloned and sequenced. Sal k 4.02 and Sal k 4.03 displayed non-conservative amino acid changes in critical positions of the IgE epitopes. Both isoforms were produced in Escherichia coli and structurally and spectroscopically characterized. Changes in the electrophoretic mobility and in their IgG and IgE immunologic behavior have been observed in comparison to Che a 2, its counterpart from C. album. Sal k 4.03 possessed a similar IgE-binding ability than Che a 2, whereas Sal k 4.02 showed a 35% reduction in the IgE binding in 86% of patients suggesting a hypoallergenic character. The three-dimensional modeling allowed us proposing which amino acid residues are involved in those immunological changes based on the epitope mapping studies previously performed in other profilins. These profilin isoforms constitutes suitable candidates for specific immunotherapy with recombinant allergens. © 2012 The Authors Journal compilation © 2012 FEBS.