BOSTON  Nearly everyone in Massachusetts is waiting for Joseph P. Kennedy II to make up his mind.

It is hard to imagine this state without a Kennedy in the United States Senate. But it seems that Mr. Kennedy, 56, an entrepreneur and a former congressman who has avoided politics for more than a decade, is the only family member seriously mulling a run for the seat his uncle, Edward M. Kennedy, held for 47 years.

For Massachusetts, with its top hospitals, universities and research centers that counted on the federal dollars that flowed from Senator Kennedy’s influence on Capitol Hill, the stakes extend far beyond its deep emotional connection with him. People here are starting to grapple with the big political question: how to replace their irreplaceable senator, whose decades of relationships in Washington made Massachusetts a prime beneficiary of the things he believed in.

“With Joe, a lot of those ties would come back quickly,” said David Gergen, a professor at the Kennedy School of Government at Harvard who has advised both Democratic and Republican presidents. “There would be an army of people who worked for his uncle who would want to work for him.”

Several people close to the family said pressure on Joe Kennedy was not coming from the family, still grieving over the loss of its patriarch, but from within Joe himself, and, they speculated, from various stakeholders in Massachusetts  mayors, labor leaders and others  who view him as the candidate most likely to inherit enough of his uncle’s monumental legacy to take care of their needs.