The E.321 was an electric locomotive built for passenger service on the line between Milan and Varese and on the Naples Metro. It had been developed as a successor of the E.320 and was also built for 650 V DC via third rail. Compared to its predecessor, it had various improvements in the electrical part and its hourly output had been increased from 1,100 to 1,450 kW. This was enough to haul a 200-tonne train with 80 km/h on an incline of 1.2 percent. The top speed was 95 km/h.

The chassis consisted of three powered axles with wheels of 1,500 mm and a carrying axle at each end. Power was transmitted from the two motors to the central axle via triangular connecting rods, similar to those used on the three-phase locomotives of the FS. The central axle had lateral play and each of the outer driving axles formed a Zara bogie with the adjacent leading axle. 17 were built by Officine Meccaniche and TIBB between 1921 and 1923. Today E.321.012 is on display at Milan.