When Arthur encounters Slartibartfast on the planet Magrathea it is explained that mice have spent a lot of their time in laboratories running complex experiments on humans, contrary to the humans thinking that it was them running experiments using mice. Slartibartfast explains to Arthur that "the business with the cheese and squeaking" was just a front for their true intelligence, and that they allowed humans to perform some "primitively staged" experiments on them in order to check how much humans had learned, and to give them "the odd prod in the right direction".
Mice were behind the ten-million-year research program to find the Ultimate Question; the research program being the Earth itself. They designed and created the Earth to be a successor to the supercomputer Deep Thought, which had found the Ultimate Answer. Slartibartfast called the research program an "epic experiment in behavioural psychology", however the mice were "furious" when the Earth was blown up by the Vogons mere minutes before the experiment would have been complete. Slartibartfast worked for the mice when they were planning to create a second Earth, and they seemed to treat him and all other beings with disdain, and were often impatient.
In the radio series, Frankie and Benjy offer Arthur and Trillian a large amount of money in return for information on the Ultimate Question. In the book and television series, these mice claim that they only way for them to get the Ultimate Question is for them to remove Arthur's brain. In the film, Frankie and Benjy are revealed to be Lunkwill and Fook, who were part of the pan-dimensional hyper-intelligent race that created the supercomputer Deep Thought. They are killed by Arthur when they attempt to remove his brain.