"When you start mucking around with election laws and start changing laws to benefit different individuals and different political parties,there's a lot of unintended consequences that end up happening as a result," state Senate Minority Leader Richard Tisei told ABC News.
Brian Walsh, a spokesman for the National Republican Senatorial Committee, reacted to Kennedy's request saying in a statement that Democrats would be playing "partisan politics" if they "reverse themselves simply because it's now politically inconvenient."
Still, some Democrats believe voters won't interpret a special temporary appointment as "partisan" since Kennedy made the request himself and since the 2004 law is relatively recent.
There is "a big blank slate here for legislators to write anything on it," said Dan Payne, a Massachusetts Democratic strategist. Payne says he expects the Massachusetts legislature will ultimately heed Senator Kennedy's wishes and amend state law to appoint a temporary replacement.
"Kennedy is that influential that they could get a special session for him," he said. But "they're not going to do anything until he's dead."
The letter from cancer-stricken Kennedy to Gov. Patrick, Senate President Murray and House Speaker DeLeo was written in July but not sent until this week.
It is an extraordinary acknowledgement that Kennedy's historic 47-year Senate career is coming to a close and recognition that a months-long vacancy could deny Democrats a key vote in the Senate.
"It is vital for this commonwealth to have two voices speaking for the needs of its citizens and two votes in the Senate during the approximately five months between a vacancy and an election," Kennedy wrote state leaders.
"Probably the most telling thing and the most troubling thing about [the letter] is it affirms that we are looking at a time when we won't have Ted Kennedy in the Senate," Massachusetts Secretary of State Galvin told ABC News.
"No one wants to openly consider the possibility that he couldn't come down for a vote if needed," said Milligan.
Given the Senator's ailing condition, that is a real possibility. Kennedy was diagnosed with a malignant brain tumor in May 2008 and was initially treated with surgery, followed by chemotherapy and radiation treatment.
Health care has been Kennedy's signature issue, and although Democrats hold a potentially filibuster-proof margin in the Senate, the fate of health care reform could hinge on a single vote.
Support for reform from moderate Democrats remains uncertain and another Democrat, Sen. Robert Byrd of West Virginia, has been seriously ill and often absent.
"They call Ted the Lion of the Senate for a reason," said Kerry in a statement. "He continues to work every single day on health care and the biggest issues of our time and every day he delivers."
Kennedy associates say the letter reflects a genuine concern by the senator over how to best serve his home state's interests and does not suggest a worsening of his condition.
"Obviously the senator is very sick," said Milligan. "The thing he's concerned most about is getting his health care plan."
Despite speculation that Kennedy's wife, Vicki, is interested in the seat, family aides have told the Associated Press that she is not interested in replacing her husband either temporarily or permanently.