The forward fuselage structure is composed of 2024 aluminum alloy skin-stringer panels, frames and bulkheads.

The crew compartment is supported within the forward fuselage at four attachment points and is welded to create a pressure-tight vessel. The three-level compartment has a side hatch for normal passage and hatches in the airlock to permit extravehicular and intravehicular activities. The side hatch can be jettisoned.

The midfuselage is a 60-foot section of primary load-carrying structure between the forward and aft fuselages. It includes the wing carry-through structure and the payload bay doors. The skins consist of integral-machined aluminum panels and aluminum honeycomb sandwich panels. The frames are constructed from a combination of aluminum panels with riveted or machined integral stiffeners and a truss structure center section. The upper half of the midfuselage consists of structural payload bay doors hinged along the side and split at the top centerline. The doors are graphite epoxy frames and honeycomb panel construction.

The aft fuselage includes a truss-type internal structure of diffusion-bonded elements that transfer the main engine thrust loads to the midfuselage and external tank. (In OV-105 , the truss-type internal structure is of a forging construction.) The aft fuselage's external surface is of standard construction except for the removable OMS/RCS pods, which are constructed of graphite epoxy skins and frames. An aluminum bulkhead shield with reusable insulation at the rear of the orbiter protects the rear portion of the aft fuselage.

The wing is constructed of a conventional aluminum alloy, using a corrugated spar web, truss-type ribs and riveted skin-stringer and honeycomb covers. The elevons are constructed of aluminum honeycomb and are split into two segments to minimize hinge binding and interaction with the wing.

The vertical tail, a conventional aluminum alloy structure, is a two-spar, multirib, integrally machined skin assembly. The tail is attached to the aft fuselage by bolted fittings at the two main spars. The rudder/speed brake assembly is divided into upper and lower sections, which are split longitudinally and actuated individually to serve as both rudder and speed brake.

These major structural assemblies are mated and held together by rivets and bolts. The midfuselage is joined to the forward and aft fuselage primarily by shear ties, with the midfuselage overlapping the bulkhead caps at stations Xo 582 and Xo 1307. The wing is attached to the midfuselage and aft fuselage primarily by shear ties, except in the area of the wing carry-through, where the upper panels are attached with tension bolts. The vertical tail is attached to the aft fuselage with bolts that work in both shear and tension. The body flap, which has aluminum honeycomb covers, is attached to the lower aft fuselage by four rotary actuators.