This invention provides C 22 substituted rapamycin derivatives of 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, {HEAD ~ diseases} of inflammation, solid tumors, fungal infections, {TAIL ~ adult T cell leukemia}/lymphomas and hyperproliferative vascular disorders 