On April 25, 2002, the Russian Soyuz TM-34 transport manned spacecraft was launched from the Baikonur cosmodrome by the Soyuz-U launch vehicle (the ISS deployment program, the mission number is 4S) that docked to the station on April 27. The crew of the Russian Visiting Expedition Three (VE-3) of the spacecraft included: Russian cosmonaut Yuri Gidzenko (commander), ESA Italian astronaut Roberto Vittori (mission specialist-1) and citizen of RSA Mark Shuttleworth (space flight participant). The launch objective is to implement a scheduled replacement of the Soyuz TM-33 rescue vehicle that was a part of the ISS from October 23, 2002, to resolve the tasks of the ISS-4 crew mission logistics support, as well as to conduct space experiments and research under the Italy program (Marko Polo project) and under the RSA cosmonaut program on board the orbital complex. On May 5, 2002, the Soyuz TM-33 descent vehicle with the VE-3 on board returned to the Earth.

On June 6, 2002, the U.S. Shuttle Endeavour STS-111 was launched (the ISS deployment program, the mission number is UF2) that docked to the ISS on June 7. The crew consisted of: NASA astronauts Kenneth Cockrell (commander), Paul Lockhart (pilot), Franklin Chang-Diaz, Peggy Whitson, ESA French astronaut Philippe Perrin and Russian cosmonauts Balery Korzun, SergeiTreschev (mission specialists). The mission objective was to deliver Expedition Five crew (ISS-5) - Valery Korzun, Peggy Whitson and Sergei Treschev - to the ISS and to return the Expedition Four crew (ISS-4) -Yuri Onufrienko, Carl Walz and Daniel Bursch - who have been operating aboard the complex since December 7, 2001, to the ground. In addition, the Endeavour delivered a remote Mobile Base System (MBS) to the station, as well as equipment for the U.S. segment, including additional Scientific Racks and consumables that were in the Italian-built Leonardo Logistics Module making its third trip to the ISS in the orbiter cargo bay. During the joint flight F. Chang-Diaz and P. Perrin performed three spacewalks in the process of which they installed Mobile Maintenance System elements on the ISS USOS, replaced Canadarm's wrist roll joint and stowed an additional debris panel on the PMA-1 adapter. Three corrections of the complex orbit were performed using the orbiter propulsion system. On June 15 the Endeavour was undocked by the crew and landed successfully to the ground on June 19.

On June 26, 2002, the Progress M-46 was launched from the Baikonur cosmodrome and on June 29 it performed automatic docking to the axial docking port of the ISS Zvezda Service Module. The spacecraft delivered 2.58 t of different cargoes, including 825 kg of fuel to support life and operation of the ISS Prime Expedition Five crew. A complex was formed consisting of: Zarya Functional Cargo Module, Zvezda Service Module, Pirs Docking Module-Compartment, Progress M-46 cargo vehicle, Soyuz TM-34 manned vehicle, S.U. Unity and Destiny Modules, Quest Airlock. The complex mass is about 153 t.
On September 24, 2002 Progress M-46 vehicle was undocked from the ISS and transferred to an orbit with a maximum altitude of 401 km and minimum altitude of 360 km, in which it traveled in a free flight under a dedicated program. On October 14, 2002 upon completion of the flight program Progress M-46 was splashed down in the assigned region of the world oceanic area.