That happens when your server is not configured to know that "index.php" is the default document name to use if one isn't specified.
Normally your hosting company will configure your server to do that for you. If they didn't, then you need to get them to fix it.
Also, if you've been editing .htaccess files to be different than what comes with Zen Cart out-of-the-box, then you may have broken the normal working operation of things.
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This problem can also occur if you have an empty file called 'index.htm' or 'index.html' in folder where the problem is occurring.
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