Nelson fired a bogey-free 65 to take the lead through 18 holes of his title defense. At 7-under-par, Nelson is one shot clear of Allen Doyle.
Two-time FleetBoston champion Hale Irwin is tied with Mike Hill, Jim Thorpe and Dave Eichelberger for third place at 5-under-par.
The FleetBoston marked the beginning of a five-week stretch that consisted of four victories for the 2000 Senior Tour Player of the Year.
Nelson has won twice this season, but hasnt claimed a title since February.
Friday at the Nashawtuc Country Club, Nelson needed only 23 putts in recording seven birdies.
The 53-year-old said prior to the start of the event that he has been suffering from lingering neck problems over the past month. He withdrew from the NFL Golf Classic after an opening-round 77 on June 8. He hadnt hit a driver until Tuesday.
Such problems are nothing new for Nelson. In his first U.S. Senior Open, in 1998, Nelson had to withdraw due to a herniated disk near his neck. He was sidelined for seven weeks.
Next week, Nelson will seek a bit of revenge as the tour moves from Concord to Peabody, Mass., for the 2001 U.S. Senior Open.
Full-field scores from the FleetBoston Classic