Police received a report at 4.40am yesterday that an 18-year-old girl had fallen ill at the Warehouse nightclub in the Byker area.
She was taken to hospital by paramedics, but her condition deteriorated and she died.
The girl has not been named, but is believed she had taken Ecstasy before becoming unwell.
Two men aged 19 and another aged 21 have been arrested on suspicion of supplying a controlled drug.
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The 19-year-olds have been released on police bail, while the 21-year-old remains in police custody.