The USS Enterprise encountered the space amoeba in 2268 while en route to Starbase 6, after diverting to investigate the destruction of an inhabited planet in the Gamma 7A system and the all-Vulcan starship USS Intrepid.
The organism created a zone of darkness in space trying to destroy all life in it.
The Enterprise crew discovered that the negative energy field was toxic to humanoid life. When unmanned probes only gave little information, Dr. Leonard McCoy suggested sending a shuttlecraft out to study the organism despite the risks of a man not coming back. Kirk agrees in defeat to send Spock out. They also found that the organism would soon reproduce by cell division. In view of the nightmarish danger posed by the organism and its multiplication across the galaxy, the Enterprise crew used an antimatter warhead to destroy it hitting its nucleus at point blank range, despite nearly being destroyed in the blast along with it. (TOS: "The Immunity Syndrome")
It was made by placing a colored liquid of several layers between two closely spaced sheets of glass, and by moving the two glasses, making the liquid undulate a little - to look like the "creature" is alive. (Star Trek: The Original Series 365, p. 236)
As evidenced by the first draft script of TNG: "Relics", the space amoeba was originally to have been referenced in that outing, with Montgomery Scott remarking to Geordi La Forge near the end of the episode, "Someday I'll have to tell you about the time we ran into a giant amoeba." However, all mention of the lifeform was eliminated from that installment by the time the final draft of the script was issued.