See also Is there a way to determine whether an e-mail reaches its destination?, my answer repeated below:
If you make the email HTML based, you
can include images in it which contain
URLs with information unique to the
recipient. You could structure your
application so that these URLs trigger
some code to mark that particular
email as read before returning the
required image data.
To be totally effective, the images
would have to form a key part of the
email, so that the recipient has to
make their email client grab the
images. You could also make the plain
text part of the email just contain a
URL to retrieve the full message,
again allowing you to track receipt.
How far you take these ideas depends on why you need to know it's been read
and to what extent you want to
potentially annoy the recipient with
an email they can't cut'n'paste, read
easily on mobile device, listen to
with a screenreader, etc...