This invention provides C 22 substituted rapamycin derivatives of {HEAD ~ the following formulas}: ##STR1## and pharmaceutically acceptable salts thereof which are useful for inducing immunosuppression and treating transplantation rejection, host vs. graft disease, autoimmune diseases, diseases of inflammation, solid tumors, fungal infections, {TAIL ~ adult T cell leukemia}/lymphomas and hyperproliferative vascular disorders 