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By default, vacation will not work properly with sendmail... you'll see errors such as the following:

"|/usr/bin/vacation username"
    (reason: Service unavailable)
    (expanded from: email_address)
   ----- Transcript of session follows -----
451 4.0.0 putbody: write error: Broken pipe
smrsh: "vacation" not available for sendmail programs (stat failed)
554 5.0.0 Service unavailable

By default, sendmail will begin queuing mail rather than sending it out at 12 load average, and stop refusing connections at 18 load average. These options can be changed in /etc/mail/sendmail.mc with the following variables:

define(`confQUEUE_LA', `12')dnl
define(`confREFUSE_LA', `18')dnl

By default, sendmail sends from a single queue. Needless to say, this is not ideal from a performance perspective. Fortunately, setting up sendmail to use multiple queues is easy!

First, create a directory for each queue you want, e.g.

mkdir /var/spool/mqueue/q{1,2,3,4,5}

Ensure that the permissions and ownerships are correct for your mail install (should be the same as /var/spool/mqueue).

Edit /etc/mail/sendmail.cf to include a QUEUE_DIR definition with a wildcard including the appropriate directories:

define(`QUEUE_DIR', `/var/spool/mqueue/q*')dnl