The Commission for Interspecies Affairs was a body within the United Federation of Planets that handled matters relating to contact with other civilizations as well as observed compliance of the Prime Directive. By the 23rd century, they were noted as being a powerful body within the Federation that was capable of applying political pressure on both the Federation Council and Starfleet.

The head of this body was the Commissioner for Interspecies Affairs who was aided in this task by the Deputy Commissioner. In 2279, the defection of Moriah Wayne to the Klingons led to the uncovering of a scandal within the Commission for Interspecies Affairs which discredited Commissioner Hightower. (TOS novel: From the Depths)