Italy's 107-time capped hooker Leonardo Ghiraldini announced the end of his international career on Sunday.
The 36-year-old's retirement follows that of 119-cap veteran Alessandro Zanni and New-Zealand-born lock Dean Budd last year.
"I say goodbye to the national team with some emotion, that jersey in the last twenty years has represented a lot for me," Ghiraldini said in a statement.
"I have represented my country at every level, from the U16 to four editions of the World Cup.
"There is a generational change that has already taken place for some time now and there are many interesting young players who are taking their place."
Ghiraldini made his debut under Pierre Berbizier in Italy's 2006 summer tour against Japan in Tokyo.
He wore the captain's armband 17 times and scored six tries for the Azzurri.
Ghiraldini was part of Toulouse's squad in 2019 when they won the French Top 14 and he has also played for English Premiership side Leicester Tigers and Treviso in his home country.
After rupturing anterior cruciate ligaments during the 2019 Six Nations he was included in the World Cup squad that year, but did not play a game as the Azzurri were knocked out in the pool stage.
His last call-up was in the Autumn Nations Cup last December in a defeat to Wales in Llanelli.
"After the injury in 2019 against France I worked at my best to get back to the top level and deserved the call-up to the national team once again," he said.
"I thank Franco Smith for offering me the opportunity, last autumn, to wear the blue jersey once again and for the confidence he would have given me again in the Six Nations which is about to start."
Ghiraldini was signed as medical cover for Bordeaux-Begles last year, but is currently without a club.
"I leave a small door open to rugby being played," he added.
"It is time for me to look beyond my professional future and that of my family."
