Repeats of the hit US comedy Friends will no longer be shown on Channel 4 and sister station E4 from autumn 2011.
The sitcom, which stars Jennifer Aniston and David Schwimmer, has been a regular fixture on the broadcaster's schedules since 1994.
Channel 4 said the move would free up funds for new shows and acquisitions.
"After 15 years, 10 hit series and 236 terrific episodes, it's time to say goodbye to old Friends and welcome new ones," said Channel 4's Gill Hay.
She added: "We are incredibly proud to have been the home of Friends for so long, but at a point when the channel is undergoing a period of creative renewal it felt like the right time to part company."
In a statement Channel 4 said it was hopeful the decision would "provide an opportunity to refresh the schedule" across both networks.
Last year it was announced that Big Brother - another long-serving Channel 4 programme - would come to an end in 2010.
Channel 4's deal with Warner Bros International Television will end next autumn, after which Comedy Central will broadcast episodes from the series.
The agreement was made after Channel 4 lost out in a bidding war with the cable channel, which the network's Jill Offman described as a "major coup".
Friends has been a huge commercial success in both the US and the UK.
The series was based around six 20-somethings living in New York and yet to figure out where their lives were leading.
As the years went on, the show charted their tangled romantic liaisons and life experiences.
The characters - Ross, Monica, Phoebe, Rachel, Joey and Chandler - spawned catchphrases, calendars, notebooks, mugs, T-shirts, video and DVD box sets and even copycat haircuts.
The last ever episode, from series 10, drew an audience of 8.6 million viewers to Channel 4 when it was screened in 2004.
Since then, the show has been on constant rotation at Channel 4 and its sister station E4, where it continues to attract an average audience of almost 400,000.