A virtual machine (VM) has direct access to an I/O device having physical and virtual functions and a mailbox register, and includes a guest driver for controlling the virtual functions. The VM runs on system software that includes a physical driver for controlling the physical function (PF) and maintains VM page tables, which include an entry that references a memory space into which the mailbox register is mapped. The system software registers a callback function with the physical driver, which the physical driver invokes upon receiving a trigger for communication with the guest driver. In response, the system software alters the page tables so that access to the mailbox register causes a PF intercept, and the callback function handles the communication with the guest driver. After completion of the communication, the system software alters the page tables so that access to the mailbox register does not cause a PF intercept.