Three children have died in a house fire in Salford, while a three-year-old is said to be in a critical condition.
A 14-year-old girl was declared dead at the scene, Greater Manchester Police said, while an eight-year-old boy and girl, seven, died later in hospital.
The blaze, which is being treated as suspicious, broke out at the terraced house in Worsley, at about 05:00 GMT. A murder inquiry is under way.
The 35-year-old mother of the children is in a serious condition in hospital.
She is heavily sedated and does not yet know her children are dead, a police spokesperson said.
Officers confirmed they had had very recent contact with the family and had visited the house in Jackson Street in the hours before the blaze. The case has been referred to the Independent Police Complaints Commission (IPCC).
Police said an "active manhunt" was under way for a suspect, although no name has been issued.
Ch Supt Wayne Miller said: "We have a suspect who we are urgently seeking in relation to this attack. All I am saying is he knows who he is and he should give himself up immediately.
"I stress that we are dealing with the murder of three children here. Any information, no matter how small, is very important to the investigation," he added.
Asked whether the tragedy was related to organised crime, the police chief said the force was "keeping an open mind", adding: "Words cannot describe what they [the family] are going through."
The four children, their mother and one other person were taken to hospital after the fire.
Two boys, aged 16, who were also in the house, were described as "walking wounded".
It is understood one of the boys is a family member. The other is not related, police said.
BBC North Tonight chief reporter Dave Guest said a neighbour at the scene told him she awoke in the early hours of the morning to hear a woman screaming and could see the red glow of the fire through her curtains.
Seven people were in the house when the fire happened, police said
The fire service said crews rescued five people when they arrived on the scene, while two people had already got out of the house.
Jackson Street between Algernon Road and Alexandra Road remains closed.
A large police presence remained at the scene and tearful locals gathered at the end of the cordons. One end is blocked by large steel barriers.
St John the Baptist church on Algernon Road said on Facebook it would open its doors between 18:45 and 19:45 for anyone "wishing a safe and quiet space to reflect on the day's events".