IBM Lotus Domino caches some database informations in it's nsf database cache to improve performance at a later hit on that database compared to the need to reopen the database, which will take longer time.
You can use the notes.ini parameter NSF_DbCache_Maxentries to control how many databases can reside in the cache at a maximum.
This NSF database cache is limited to 10000 entries from 5.x to 6.x. Note that the documentation for NSF_DbCache_Maxentries incorrectly lists a maximum of 2000 entries.
Beginning with IBM Lotus Domino 7.0 the maximum value has been increased by 100% to 20000 entries.
To optimize your servers configuration you can check your servers statrep.nsf to see how many databases reside in the cache at peak times. If you hit your configured maximum value, look at the Database.Database.BufferPool.PerCentReadsInBuffer value. If this value is lower than 97% you may consider raising the maximum number of databases in the nsf cache.