Gavin Grant, chief executive of the RSPCA, has stepped down with immediate effect because of medical concerns.
Grant joined the RSPCA as chief executive in January 2012 and the charity said in a statement today that he had been "instrumental" in raising its profile and laying the foundations for its long-term development.
Grant was on his second stint working for the charity, having also been its director of communications and campaigns between 1988 and 1991.
In the interim, the charity said, John Grounds, director of marketing and campaigns, would represent the charity externally and cover its public commitments.
Ray Goodfellow, chief legal officer, and Michael Ward, director of resources, will carry out the charity’s work at a senior level with the support of its other directors and trustees, the charity said.
In a statement about his departure, Grant said today: "It has been a huge honour to have held this post. The RSPCA is a magnificent organisation at the heart of what is the very best in humanity. The society is blessed with great people, both paid and volunteer. I wish it well as it continues to face huge challenges in ensuring it is ever stronger and able to meet the needs of our fellow creatures."
Mike Tomlinson, chair of the charity, said: "I would like to take this opportunity to thank Gavin on behalf of myself and my fellow trustees for the very significant contribution he has made to the society for a second time in his career."
The RSPCA declined to give any further details on the nature of Grant’s health concerns.
The charity has come under significant pressure from right-wing newspapers during his time as chief executive.
In December 2012, it came in for sustained criticism from some elements of the media and pro-hunt campaigners over its successful private prosecution of the Heythrop Hunt, which cost the charity more than £320,000.
It was accused by a cross-party group of MPs of of bringing a politically motivated prosecution and failing in its duty of prudence, but was cleared of any wrongdoing by the Charity Commission.
The charity then complained to the Press Complaints Commission about what it called "potentially defamatory" coverage by The Daily Telegraph, but its complaint was not upheld.
Later in 2013, the charity was forced to defend itself from accusations that it was misusing the justice system and wasting court time after a prosecution of suspected badger digging was dropped.
An internal memo written by the charity’s former deputy chairman in September said the charity could be seen as "too political" by the public and risked losing its best staff.