To achieve high performance, it was decided to adopt a symmetric compound engine (a Von Borries design), with the two inside high pressure (HP) cylinders having the motion for their valves derived from the outside Walschaerts valve gear; this was unusual for Italian locomotive practice, where the compound engine had been shelved once the superheating technology had become available in the 1910s.

[2] The Class 746 initially operated on the Milan-Bologna-Florence-Rome-Naples main line; after portions of it were electrified, they served on the Milan-Turin and the Milan-Brescia railways.

While fast, powerful and suitable for both fast passenger and goods trains, the Class 746 proved difficult to start and somewhat uneasy when running at or close to its top speed (with both problems originating from its compound engine); also, at higher speeds the low-pressure cylinders contributed relatively little to the locomotive's power output.

[2][3] Their poor riding qualities and their huge mass (for Italian standards) led some Milanese crews to nickname them "Krassin"[a].

In 1932, four locomotives, two with Walschaerts valve gear (the 746.007 and the 046) and two with Caprotti valve gear (the 746.107 and the 108), were modified with a simple-expansion engine; while results were very encouraging, with the modified locomotives being as performant as the unmodified ones but performing better at higher speeds, the widespread electrification meant that this experiment was not followed up with more conversions.