The organisation's office for the planned systematic killings of patients was initially housed in the Columbus House at the square called Potsdamer Platz in Berlin from the autumn of 1939. Since April 1940, the head office was located in a villa at Tiergartenstrasse 4, where more than sixty doctors, administrative staff, drivers and craftsmen worked on organising and implementing the patient murders. Their hiring was a result of free recruitment, service obligation or secondment. Executive members of staff had to prove they were in favour of the National Socialist ideology and the aims of the »euthanasia« programme. When they were hired, the employees were sworn to secrecy.

The main office of the organisation consisted of six departments. The Medical Department was responsible for all medical issues, the medical experts, the processing of registration forms and the records office. It was first headed by Werner Heyde (1902–1964) and then Paul Nitsche. The Administrative Department under Friedrich Tillmann oversaw the bureaucratic processing of the patient murders in the killing centres. The Central Finance Department was responsible for procurement and finances. The Transport Department compiled the transport lists and organised the transfer of the patients to the killing centres. The Personnel Department took care of the staff in the killing centres and in the head office in Berlin. The Inspector's Office set up the killing centres and monitored them. Lawyer Dietrich Allers was responsible for the internal running of the T4 office as of January 1941.