I ran into something like that on my desktop system when I was testing out Streets & Trips. I have the Palm Desktop installed, which I use for sync'ing my Garmin iQue (a Palm OS-based PDA/GPS). The Hotsync program, which is running all the time, was conflicting with the USB-to-Serial driver. As soon as I told Hotsync to exit, the problems just went away.
Example, with Hotsync running, when I launch GPSGate it immediately shows there is no GPS connection, even if the GPS is connected. If I exit GPSGate, exit Hotsync, and run GPSGate again it sees the GPS signal immediately. Once I'm done with the GPS I just run Hotsync again. If I forget to run it, no harm. I just run it the next time I need to sync my PDA.
If you aren't using Hotsync to sync a PDA, perhaps you have some other resident utility that grabs the USB or Serial ports.
...ken...