S-49 remained at Bridgeport through July 1922, but in August 1922 she moved down to the Submarine Base at New London, Connecticut, where she joined Submarine Division Zero, composed of units engaged in submarine research and development.[1] Later reassigned to Submarine Division 4 and then to Submarine Division 2, she continued experimental work, including aerial visibility tests and torpedo development, and also participated in regularly scheduled exercises, primarily in the New London area, into 1926. At the end of January 1926, she proceeded to Portsmouth Navy Yard at Kittery, Maine, for a regular overhaul.[1]
On 2 April 1926, S-49 returned to New London, but on 20 April 1926 her operating schedule was again interrupted. At about 07:50 that morning, S-49’s engines were started. Seven minutes later, just as a pilot cell cover was removed to test the specific gravity of the electrolyte, the forward battery exploded. The hydrogen gas explosion destroyed the battery cells in the forward half of the battery and forced up the battery deck. Ten men were injured, two others were gassed during rescue operations, and four of the twelve died of their injuries. The battery compartment was sealed and kept shut until mid-afternoon on 20 April, when the outboard battery vent was opened. During the night, the submarine took on a slight list to port and S-49′s crew used air pressure to keep ballast. At about 05:15 on 21 April, a second explosion occurred in the battery room when wash from vessels departing for torpedo practice rocked S-49. The compartment was resealed for another few hours, after which the work of clearing the wreckage was begun.[1]