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Alpha-sarcin is a cytotoxic protein composed of a single polypeptide chain. This protein shows a significant degree of amino acid sequence similarity with a group of several phylogenetically related fungal ribonucleases. The leading member of such a group is ribonuclease T1. Three proteins of this group, ribonucleases T1, Ms and F1, are well known in terms of their crystal structures. These data have been used to propose a conformation for α-sarcin. The secondary structure of the cytotoxin would contain one α-helix segment as well as around six β-strands and 14 β-turns. The folding of these structural motifs is proposed by comparison with the three-dimensional structure of the three proteins from the ribonuclease T1 subfamily. The four longest β-strands of α-sarcin would define an antiparallel β-sheet structure resulting in a highly hydrophobic domain. The predicted folding for α-sarcin is discussed in terms of the ability of this protein to electrostatically and hydrophobically interact with phospholipid vesicles. The proposed conformation would explain how a highly polar protein, such as α-sarcin, can produce membrane destabilization resulting in protein translocation across lipid bilayers.