Fire crews responded to the 7300-block of South Marshfield Avenue sometime before 6:55 a.m. for a reported blaze.
Two people were taken to University of Chicago Medical Center after suffering smoke inhalation in the incident, fire officials said.
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CFD did not immediately provide their conditions or any additional information about how the fire might have started.
Firefighters could be seen extinguishing flames on the home's roof after 7 a.m. The fire drew a large emergency response to the South Side neighborhood.
This is a developing story; check back with ABC7 Chicago for updates.