The first ship to have her passengers quarantined on the island was the steamship China on April 27, 1891:   there was smallpox on board.  When the passengers reached the station, they were checked by a doctor, then they bathed with carbolic soap, and donned overalls furnished by the attendants.  Their clothing and baggage were sent through large metal cylinders where it was disinfected with live steam under pressure.  The passengers were then assigned to barracks for a fourteen day quarantine.  Their barracks were fumigated with sulfur dioxide and flushed with salt water every morning.   Ships were fumigated with live steam; later such chemicals as cyanide and burning sulfur were used.

As years passed, use of Quarantine Station diminished. Better medical examinations were made at ports of embarkation, and improved medical practices made lengthy quarantines unnecessary. Being an island isolated from the mainland made the station inconvenient and expensive to maintain. It was abandoned when the U.S. Public Health Service, which succeeded the old U.S. Marine Health Service, moved to San Francisco in 1946. Most of the quarantine buildings were torn down in the late 1950s, after Ayala Cove area became a state park. Those remaining include the former bachelor officers quarters (now a park museum) and the surgeon's and assistant surgeon's homes which are now used by state park personnel.

Photos of the quarantine station are available here.