The Leukemia and Lymphoma Society just saw its e-mail list slashed from 33,636 addresses to 4,510 and the organization’s director of eMarketing is happy about it. And contrary to what many marketers are probably thinking right about now, the man doesn’t sound like a crackhead.

Last year, the LLS—an organization dedicated to blood cancer research, education and patient services—found that 30% of its subscribers weren’t getting its four monthly newsletters because some of LLS’s e-mail was being blocked. The problem: too many spam complaints.

As a result, on a recommendation from its service provider, ExactTarget, the LLS agreed to re-confirm permission from its entire e-mail list.

“There was really no point in us having a giant list of people who were not responding,” said Chris Harris, who joined the organization as director of eMarketing about a year ago. “What I inherited was a large list that was sitting there with not a great open rate and a pretty bad click-through rate. I just decided one day that we really need to clean this list up.”

Spam complaints are the No. 1 factor large inbox providers, such as AOL, Microsoft and Yahoo!, use to determine whether or not to block incoming mail. As a result, where the high cost of paper and postage drive marketers to exercise list hygiene in direct mail, user complaints are emerging as a hygiene-disciplining factor in e-mail marketing. Marketers are increasingly faced with either limiting user complaints by removing inactive addresses or getting their messages blocked.

Still, the idea of getting permission again from people who have already given permission to receive e-mail isn’t one most marketers—most of whom strive to grow their lists, not trim them—readily embrace.

However, though it may cost little to send e-mail to non-responsive people, mailing to inactive names hoping for an incremental increase in purchases invites more trouble than it’s worth, according to Chip House, vice president of privacy and deliverability at ExactTarget. “Why would you want to send to anybody that probably isn’t going to respond?” said House. “Why would you want to take the chance that he’s going to complain?

There are also ways to “re-engage” people that are not as stark as simply reconfirming permission to e-mail them, he said. For example, a marketer may want to reduce the frequency of the e-mails to inactive recipients to see if that re-engages them.

He also said reconfirming the whole list is a drastic measure. “In most situations, you’re culling off a portion of your list, say, people who haven’t opened or clicked in 90 days, or maybe a portion of your list that came from your brick-and-mortar stores and you don’t trust the way the names were captured.”

The LLS’s Harris said he wrestled for months with the decision to re-opt in his entire file. “Your gut instinct as a direct marketer tells you that this is not what you want to do,” he said.

Though the LLS’s e-mail list was drastically cut in terms of size, after the re-confirmation, spam complaints dropped from 27 or 0.51% per campaign to zero, according to ExactTarget. Also, the list’s average open rate rose from 25.2% to 53.1% and the average click-through rate rose from 6.6% to 21.5%, according to ExactTarget.

Most surprisingly, total clicks per campaign were virtually unchanged at an average 509 before the re-confirmation and 510 afterward.

“For us, because of the nature of what we’re sending out, we really wanted only the people who are interested in what we had to say,” said Harris.