Best practices - should I order newsletter recipients by email host or not?

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For a newsletter mailing, about 50,000 users, using pear, is it convenient to order the list by mail provider or leave it all randomly?

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From my experiences using Exim to send large amounts of emails, performance will suffer heavily if your email queue grows too large. Depending on your hardware, once you have around 10,000 emails in the queue, you will start to see significant effects of bogosorting, where the server uses more CPU just juggling the queue than actually getting any useful work done.

One way of avoiding large queues, is of course to get the emails delivered as fast and efficient as possible. One of the many ways of achieving this, is to get Exim to deliver multiple emails over the same TCP connection. This in turn can be achieved by sorting the recipients by domain, but that is not enough! By default, Exim will try to deliver each mail it receives immediately and then each delivery will open its own connection (this gives fast deliveries for very small volumes but will drive server load through the roof for larger volumes). You need to first spool the mails to Exim, and then let a queue runner handle the actual delivery which will then automatically see all other emails in the queue that should go to the same host and will deliver them over the same connection.

Optimizing Exim for sending large amounts of emails is a very complex subject that cannot be solved with just a few magical tricks. Crucial configuration options are (but not limited to): queue_only, queue_run_max, deliver_queue_load_max, remote_max_parallel, split_spool_directory, but also fast spool disk, enough RAM, and making sure Exim starts new queue runners often enough (command-line option when starting the Exim daemon).

How this relates to PEAR escapes me, but perhaps this gives you some ideas of how to approach your problem.