The Arizona Cardinals were informed they would be wise to proceed without Manning as a candidate to join the team and will now retain quarterback Kevin Kolb, paying him a $7 million roster bonus due after a Friday deadline of 4 p.m. ET.
That leaves three teams as finalists to sign Manning, including the Tennessee Titans.
Talks with the Miami Dolphins were described as "positive," but he informed them midweek they were not going to be among his finalists, sources said.
Now San Francisco is the sleeper team few were expecting.
Manning worked out for the 49ers on Tuesday night at Duke in Durham, N.C., with coach Jim Harbaugh and offensive coordinator Greg Roman witnessing a passing session that was described by a source as "very impressive" -- enough so that the 49ers sent a doctor to Durham to conduct a physical exam Wednesday.
Once Manning works out for the Titans, the process of football discussions, medical reviews related to his neck surgeries, physical workouts and parameters of a contract will be in place for the quarterback to make a decision on his next team.
There is no known deadline for Manning's decision, but the process has been exhaustive since he was released March 7 by the Colts. Before Friday's visit with Denver, it was Manning who insisted upon working out for the teams, endorsing the integrity of the process.
Manning first visited the Broncos March 9, followed by a visit to the Cardinals, but there were other unreported developments last weekend, such as the Seattle Seahawks parking a jet at an airport in the Denver area in a failed attempt to visit with the quarterback, according to sources.
Manning returned to Indianapolis after his Arizona trip to get an updated MRI on his neck. It was in Indianapolis where he visited with Dolphins coach Joe Philbin and offensive coordinator Mike Sherman. Sources also say Manning had a meeting with Dolphins owner Stephen Ross in Durham, where he has spent time working out at Duke.
The majority of teams that were provided with the latest medical data, including their own physical exams and extensive quality video of Manning's throwing sessions at Duke, had informed the quarterback that it was not necessary for him to physically work out for them.
While contract parameters have been discussed, extensive negotiations involving contract language also must be completed. Sources say that Manning will provide any team that signs him with appropriate financial protection in the event he suffers a setback related to his prior neck injuries.
Cartwright, the former Raiders and Redskins running back and special teams standout who signed a one-year contract with the 49ers on Friday, still believes Alex Smith will be the 49ers' starting quarterback -- or at least he's speaking as if that's the case.
"I think Alex is a great guy. I think we've got a great quarterback in Alex," Cartwright said, according to The Associated Press. "Whoever is there, we'll be there to support him. Right now Alex is the guy."
The 49ers have been working to re-sign Smith, the No. 1 overall draft pick in 2005 who made a comeback in 2011 under first-year coach and former NFL QB Harbaugh, and Smith has acknowledged he was happy with their three-year offer.
Manning and Smith both are represented by agent Tom Condon and CAA Sports.
Neither tight end Vernon Davis nor running back Frank Gore had been told by the 49ers they were pursuing Manning. Both have publicly supported Smith during his up-and-down seven-year tenure with the franchise.
When asked if Smith is still the man, Gore said, "I think he is."
The NFC West champion 49ers on Monday signed wide receiver Randy Moss after he spent a year out of football, hoping he will be the dynamic wideout and deep threat of his past to open up the field.
"Rock has been a standout special teams contributor, who has also shown versatility at the running back position," 49ers general manager Trent Baalke said. "He has all of the intangibles that we look for in a 49er."
Chris Mortensen is a senior NFL analyst for ESPN. Adam Schefter is ESPN's NFL Insider. Information from The Associated Press was used in this report.