As stated by protagonist Arthur Dent in the novel The Restaurant at the End of the Universe (1980), upon discovering that the Ultimate Question may be "What do you get if you multiply six by nine"?
"Six by nine. Forty two." "That's it. That's all there is."
"I always thought something was fundamentally wrong with the universe."
The explanation is that 6 times 9 is the question to life the universe and everything, and the answer is 42, because humans have been using the wrong base system for mathematics. That is why mice are the smartest creatures on the planet. If you use base 13 and multiply 6 by 9 you will get the answer 42, which after all is the true base of mathematics in the Universe and used by all intelligent lifeforms, which excludes humans by definition.
Ah, no. Douglas Adams himself stated that the "question" has nothing to do with base-13 arithmetic. After all, we lowly humans are quite capable of doing calculations in base-13, but that doesn't bring us any closer to understanding the nature of the universe.
The ultimate question is not "What do you get if you multiply six by nine?" That was simply a corrupted version of the question encoded in Arthur Dent's brain patterns. The complex biological computer program (also known as "the Earth") which had been calculating the question for millions of years got screwed up when the Golgafrinchans arrived on prehistoric Earth and destroyed the environment.