1. When it seems that you are not receiving any new mail, does the ISA server stops listening on port 25? (netstat -a | more, or you can use an dial in to your ISP and see if you can telnet on port 25 to your ISA server's IP address).
2. when mail is not being recieved, is it from a particular domain or any domain (what i mean is, there is no mail flow period or does it depends on the domain from which the mail is being sent).
3. If it happens often, you can run Network monitor to capture the traffic on the outbound nic and on the inbound nic to see where the problem is, it could be that your mail server (Lotus, Exchange, SendMail etc) is getting overloaded and drops the connection to the ISA server.
4. If you are running Exchange 2000, please make sure that the GC it is talking to is always available, I know from experience that if the GC that Exchange 2k talks to is not available or is having intermittent communication issues, all hell breaks loose on Exchange.
5. Do you have a Firewall between ISA and the Internet connection? Could it be an issue there?