Also, you could check your power settings. Normally, Apple has the HD going to sleep whenever it isn't being used. This cycling from sleep to on can cause HD spin-up noises and clicking. The clicking is actually the read/write head, its docking and undocking to access the HD.
Another thing you can do is see if your free memory is too low. If you run out of main memory, your computer will start thrashing, which means it is using only virtual memory (your HD) to read/ and write data to, which causes the noises to happen very often. So following frdmfghtr's advice, check the CPU% and the memory usage of apps.
If you set your HD to never sleep, you shouldn't get as many clicks and spin-ups and downs, but this could potentially lead to shorter HD life, and since iBooks are meant to be portable, the more work the HD is doing, the more moving parts, and the more the risk for mechanical failure (or worse, a head crash on the HD platter).
Hope this helps....