The 14-year-old girl was taken to hospital along with another girl aged 13 after they were both found unwell in a house on North Marine Road in Scarborough yesterday afternoon (Wednesday), North Yorkshire Police said.
Very sadly, the 14-year-old was pronounced dead at hospital a short time later.
The 13-year-old remains there for treatment although police have said her condition is not thought to be life-threatening.
Two teenage boys have been arrested on suspicion of offences including supplying Class A drugs. One remained in custody this afternoon, while the other has been released under investigation.
The force has described it as a "devastating incident", issuing a warning to anyone who has acquired MDMA or other illegal drugs.
Detective Chief Inspector Graeme Wright, of North Yorkshire Police, said: “First and foremost, our thoughts are with the family and friends of the young girl who died as a result of this tragic event, and of all those affected by it.
“Extensive police enquiries are ongoing to determine the events around her death.
“Although our investigation is at an early stage, I would urge anyone who has acquired MDMA or other illegal drugs recently not to take them. If you have taken such a drug and feel unwell, it is vital that you seek medical help immediately.
“This is clearly a devastating incident, and I would ask everyone to respect the privacy of the families involved, and refrain from speculating about this incident online.”