There are a few different reasons that you can run into this message:
We updated our codebase quite drastically in March 2020. As the result of no shared code between the old and new site, the API changed, both in response format and urls. You need to update your application to use the new API urls and response formats.
If you are making requests to endpoints that are not plurals, then you fall under this category. Please visit the wiki for the most up to date information. Do not use some random "documentation" you found on github, it is out of date and incorrect.
You likely can't resolve this problem yourself, as the application you are using needs to be updated. Please contact the author, or find another, more up to date tool.
If you are attempting to use the API you may be seeing this if your user agent is not in line with our user agent policy. The default user agent for many programming languages and libraries have been blocked for abuse. DO NOT USE A BROWSER USER AGENT FOR API TOOLS - YOU WILL GET MANUALLY BLOCKED. You've been warned. Please see the wiki page for the API for additional details.
If you repeatedly see this message you should stop all access attempts and contact us so that the problem can be resolved.
If none of the above apply to you, then you have likely been blocked manually after review. These blocks DO NOT EXPIRE. You will need to contact us to have it removed.
You can reach us at management (at) e621 (dot) net
Please include your ip address, the time you received this message and what you were doing at the time. We will respond as quickly as possible.