You can create a web service that your customers can call to pass you the Xml data.
Firstly you need to create a schema to define the message formats, both request and response. Then create an orchestration with a request response port (make this public) to receive the Xml message and return a response. In your orchestration perform the required logic to update the mainframe (HIS integration?, flat file creation? …). Then generate the response message.
Once you have built this solution you can use the Biztalk WCF publishing Wizard that will generate the IIS virtual directory. You can either use the schema definitions and construct your interface or you can use the orchestration port