A self-test method and system for facilitating reliable and fault-tolerant operation of a multi-peripheral-device enclosure for use in high-availability computer systems. The reliable and fault-tolerant multi-peripheral-device enclosure uses a three-tiered port bypass control strategy for diagnosing and isolating malfunctioning peripheral devices within the multi-peripheral-device enclosure, and uses a similar a three-tiered port bypass control strategy for isolation of the entire multi-peripheral-device enclosure from a communications medium that interconnects the multi-peripheral-device enclosure with one or more host computers. This three-tiered port bypass control strategy is employed by a self-test routine to isolate the multi-peripheral-device enclosure from external processing elements in order to test peripheral devices and other components within the multi-peripheral-device enclosure, and to isolate any detected defective or malfunctioning components.