The class was initially assigned to the line between Paris and Marseilles, hauling services including the famous Le Mistral expresses, but within a few years they were displaced by electrification. Most of the class was then transferred to the Nord, l'Est and l'Ouest regions. For over ten years they managed the traffic on the line west of Le Mans, including the 411 km (255.4 mi) line to Brest and 410 km (254.8 mi) line to Quimper. They hauled trains of up to 16 coaches, weighing over 800 tons.
The 241.P class were allocated to the following depots:
- South-eastern Region: Dijon, Marseille-Blancarde, Lyon-Mouche, Nevers
- Eastern Region: la Villette, Noisy-le-Sec, Chaumont
- Northern Region: La Chapelle
- Western Region: Le Mans
Although powerful, the class was not without its problems. The frames, lightly constructed to avoid excessive axle load, were not able to handle the power of the cylinders and flexing of the frame under load led to problems such as hot axle boxes. The class also suffered from leaking boiler tubes after passing over points, which necessitated structural reinforcement.
These impressive-looking locomotives, with their compound drive and eight coupled wheels, were withdrawn progressively from service from 1965 for 241.P.1 to 1973 for 241.P.16. Their last regular work, on the Le Mans to Nantes route, ended in early 1970. The class was nicknamed the grosses P to distinguish them from the 141.P Class, which were called the petites P.
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