I am trying to control my whole house audio system using the serial communication. I can connect my computer (Mac) through via USB through a USB->Serial (pl2303) adapter and send/receive on the line.

I have tested that my mbed can communicate through the serial connection (not over the usb in the mbed) through a Max3232 (http://www.mdfly.com/index.php?main_page=product_info&cPath=9_41&products_id=295) connected to my Mac's serial (serial to USB) port just fine.

But when I connect that same connection to my audio system I get nothing. Any ideas? What could possibly be going on here? Is it that my Serial->USB converter is able to handle lower voltage differentials then the audio device can handle. What is the best way to debug this?

perhaps the audio system needs use of RS232 signals that aren't implemented in the USB/Serial or because of USB don't have the correct timing? Such as RTS, CTS, DTR, DCD, and so on. Or vice-versa, only the bare minimum are needed: GND, TXD, RXD are used. You may need a NULL MODEM which is simply a wiring swap of TXD and RXD.