Firefighters were alerted to the blaze on Parsonage Road, in Withington at 2.20am.
A neighbour told the Manchester Evening News she was woken by screams and saw thick, black smoke billowing from the house.
A man and four children have been taken to hospital after a fire at a house in Withington, Greater Manchester.
A Greater Manchester Police spokesman said the three girls and a boy were being treated in hospital for their injuries.
The man is in a serious condition, while the condition of the children is not known.
Greater Manchester Police said officers were investigating the cause of the blaze in conjunction with the fire service.
'We want to speak to anyone who may have witnessed the fire, or were in the area in the hours before the fire'.
Anyone with information is asked to contact police on 101 quoting incident number 140 10/02/17 or Crimestoppers, anonymously, on 0800 555 111.