The Me.410A-1/U4 and the Me.410A-2/U4 became the most powerful armament available in Me.410A modifications. They provided a 50 mm Rheinmetall BK 5 cannon. This weapon was initially developed as an antitank gun, with a 21-round drum magazine and a pneumatic reloading system, and was mounted in the bomb bay. The presence of the BK 5 cannon had no discernible effect on piloting the aircraft; however, the Me.410's flight characteristics were slightly reduced due to increased aerodynamic resistance. Tests showed that an aircraft with the 50 mm BK 5 cannon was able to target T-34 and KV tanks as well as railway carriages, steam locomotives, and small waterborne vehicles. However, it turned out that the standard Revi 16 sight was not suitable for firing the new weapon, so planes armed with BK 5 cannons were fitted with ZFR 4a gun sights.
Firing practice showed that the BK 5 cannon frequently failed when firing long bursts (more than five shells). This problem was solved when a special automatic breaker limiting bursts to three rounds was introduced into the fire control circuit.
The Me.410A never became an anti-tank aircraft; instead, the Hornets armed with the 50 mm BK 5 cannons targeted American heavy bombers. Firing tests targeting B-17 and B-24 bombers that had been forced to land in German territory showed that a hit with only one 50 mm shell was usually enough to destroy a bomber.
The principal beam, one of the most durable structural members of the aircraft, was easily destroyed with a hit from one of the shells. The bombers' fuel tanks, which were safely protected with sponge rubber from any through shots from small-calibre weapons, would detonate when hit by BK 5 cannon shells, turning large pieces of the skin and the airframe of the wing inside out. In theory, German pilots could shoot down enemy planes while remaining out of the reach of their defensive fire. But in real combat conditions it was not easy for Me.410 crews to win duels with the escort fighters, not only with the newest P-51 Mustangs but also with the P-47 Thunderbolts and the P-38 Lightnings.
50 mm BK 5 cannons were installed on Me.410A-1/U4s on the front, replacing the 20 mm Mauser MG 151/20 cannons and 7.92 mm Rheinmetall-Borsig MG 17 machine guns. The Me.410A-2/U4 "destroyers" ("Zerstörer") were equipped with BK 5 cannons directly at the factory and retained all of their standard armament.