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In 2000, the character Matt Musgrove (played by Kristian Ealey) transferred from Brookside (1982) to Hollyoaks, the first time this had been done in a British television soap opera. Ealey died in 2016 aged 38.

Alex Carter (Lee Hunter) auditioned for the part of Darren Osbourne, but he lost out to Ashley Taylor Dawson. About four years later he was up for the part of Dan Hunter, but was considered to look too young for that part, but ideal for the younger brother.

The series is very famous for its attractive young cast. From 2001 to 2012, the male stars would release a "Hollyoaks Hunks" calendar and the female stars would release a "Hollyoaks Babes" calendar, in which the actors and actresses would pose in swimming costumes or underwear.

In 2013, executive producer Bryan Kirkwood refuted accusations from critics that actors were cast for their good looks. He said they "always cast on acting ability before anything else".

Although set in a fictional village in Chester the series is actually filmed in Liverpool and uses many of the same houses used by Brookside (1982).