2-Substituted 2-aminoethanol was shown to be the minimum essential structure for the immunosuppressive activity of ISP-I (myriocin, thermozymocidin) by simplification of 2 substituted 2-amino-l,3-propanediol, which was generated by modification of ISP-I. Among the series, 2-amino-4-(4-octylphenyl)butanol hydrochloride displayed comparably potent activity to 2 amino-2-[2-(4-octylphenyl)ethyl]- 1,3-propanediol hydrochloride, FTY720.We isolated the immunosuppressant ISP-I 1 (1: myriocin 2, thermozymocidin 3) from the culture broth of Isaria sinclairii (ATCC 24400). The structure-activity relationships of ISP-I derivatives 4 and mycestericins 5, which were isolated from an ISP-l-producing strain, Mycelia sterilia (ATCC 20349), showed that the 2-substituted 2-amino-l,3-propanediol 6 structure was the key basic structure for potent immunosuppressive activity. Furthermore, modification of the hydrophobic part indicated that the 2-(4-octylphenyl)ethyl group was optimum, affording the potent immunosuppressant, FTY720 (2) 7. However, modification of the hydrophilic part had not been examined. In this paper, we report that further examination of the hydrophilic part in the 2 substituted 2-amino- ! ,3-propanediol led to the identificatin of 2-substituted 2-aminoethanol as the minimum basic structure for the biological activity.