This paper deals with the investigation of the performance of distance protection in a 400 kV transmission line for a system with high penetration of photovoltaic sources (PV). A grid with a PV plant is designed in RSCAD software environment, which is supported by RTDS. By performing hardware-in-the-loop tests, two commercial relays are investigated in real-time. Firstly, the distance protection function is tested with a synchronous generator to check the response of the studied system and validate correct relay settings. Afterwards, the synchronous generator is replaced by a generic PV plant model. The impact of different fault locations, fault types and fault impedances are studied. Finally, the critical scenarios in the power system are determined for which a relay fails to detect a fault. Many simulations are performed and cases, when a relay unexpected operations, are identified. Relevant solutions to overcome these problems are suggested.