Cladosporium herbarum is a fungal plant pathogen. Its hosts include Bryum, Buxbaumia, Gyroweissia, Tortula, and Dicranella. The ascomycete Cladosporium herbarum is a prominent fungal inducer of Type I allergy. The only major allergen identified so far is Cla h 8, a NADP-dependent mannitol dehydrogenase (MtDH). MtDH, a cytoplasmic protein of 28. 5kDa, belongs to the Short chain Dehydrogenases/Reductases (SDR), acting as a NADP-dependent oxidoreductase. In this study, we found that C. herbarum MtDH can exist as monomers, dimers and tetramers in solution and, correspondingly, forms tetramers and higher oligomers in two crystal structures. The formation of oligomers and higher multimers of MtDH provides a missing link to its allergenic properties. We can also clarify the atypical enzymatic properties of MtDH by two alternative binding modes of the substrate to the active site.