The health bill is currently working its way through ParliamentThe unions representing nurses and midwives have joined others in stating their "outright opposition" to the government's NHS plans in England.
The Royal College of Nursing and the Royal College of Midwives had expressed concerns in the past, but said they were willing to work with ministers.
However, now they want the entire bill covering the changes to be dropped.
The government said it was disappointed as the bill would "empower" front-line staff to take charge of improving care.
The colleges' stance comes after a similar move by the British Medical Association last year.
It also mirrors the stance adopted by Unison, which represents a host of administration and support staff, such as porters.
The Health and Social Care Bill is still working its way through Parliament.
It is currently in the House of Lords and will be returning to the Commons soon, but changes are already being made on the ground to pave the way for the new system which kicks in in 2013.
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