An explosion occurred when a process vessel was overpressurised during a process upset because a manual valve in the pressure relief vent had been left closed. Originally, it was intended to be normally left closed as a maintenance isolation valve, but a process change required it to be operated on a regular basis. Our investigation revealed that the original design basis was correct and that there had been no proper assessment of the change of use. There was no safeguard against human error because the procedure for locking the valve and checking its position had fallen into disuse.