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His death comes a week after the death of Bobby Sands on 5 May, the first to die in a republican campaign for political status to be granted to IRA prisoners.
Hughes began refusing food and medical attention a week after Sands began his hunger strike on 1 March. He lapsed into unconsciousness and died at 1743BST today.
As news of his death spread in Catholic areas of Belfast and Londonderry, women clanged dustbin lids and young men stoned army vehicles, threw petrol bombs and hijacked lorries.
Hughes's brother, Oliver, blamed the Prime Minister, Margaret Thatcher, for his death. Speaking from his hometown of Bellaghy he said: "Margaret Thatcher and the British Government have murdered my brother and his blood is on Margaret Thatcher's hands."
The condition of two other hunger strikers at the Maze, Raymond McCreesh and Patrick O'Hara, continues to deteriorate.
Their five demands include: the right to wear their own clothes, refrain from prison work, associate freely with other republican prisoners, to have visits and parcels once a week and the right to have lost remission on sentences restored.
Security forces have said Hughes was "an absolute fanatic whose name stood for murder and nothing else".
A spokesman went on to describe him as "as vicious a man as you could meet, a ruthless killer who thrived on what he was doing".
His republican colleagues hailed him as "fearless and active".
Four years ago, Hughes became a wanted man after the home of a policeman was blown up in County Tyrone.
No-one was hurt but Hughes' fingerprints were found on adhesive tape used on the bomb.
In March 1978 he was finally caught after a gun battle at Bellaghy and eventually sentenced to a total of 83 years in prison for his six-year-long career as an IRA gunman and bomber.
The government is refusing to grant any of the hunger strikers' demands. Mrs Thatcher says they are a cover for gaining political status, a special category denied paramilitaries in the Maze since 1976.
The Maze Prison was initially run along the lines of a prisoner-of-war camp, segregated according to paramilitary allegiance with military-style command structures.
In March 1976 the British Government ended special category status - which had accorded the prisoners political recognition - and started to treat paramilitary offenders as ordinary criminals.
The jail became the focus of intense international scrutiny between 1976 and 1981 when Republican inmates fought for political status, initially through the "blanket" and "dirty" protests.
Their campaign culminated in two hunger strikes.
During the second in 1981, 10 Republicans, led by Bobby Sands, starved themselves to death and 64 civilians, police and soldiers died in violence directly attributable to the hunger strikes.
Three days after the hunger strikes came to an end on 3 October, Northern Ireland Secretary James Prior negotiated a package of concessions for the Maze prisoners - much to the fury of the loyalist community.
He met two of the prisoners' demands - the right to wear their own clothes and the restoration of 50% of lost remission for those who obeyed prison rules for three months.
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