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Sergeant Tony Woodbridge, of Oamaru, said police were called to a crash at the intersection of Eden and Aln Sts at 6.30pm.
Crews from the Oamaru Volunteer Fire Brigade cut the 91-year-old woman from her vehicle.
''Early indications show that somebody has failed to give way at the give way sign,'' Sgt Woodbridge said.
Eden St, between Reed St and Aln St, was closed from 6.30pm while the serious crash unit from Dunedin investigated.
The Oamaru woman was in a serious condition and was airlifted to Dunedin Hospital.
The other driver, a 22-year-old Oamaru man, was checked by St John, but was uninjured.
Sgt Woodbridge thanked the two members of the public who rushed from a nearby takeaway restaurant to the woman's aid and waited with her until emergency services arrived.