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I have installed Xamarin Studio 4.0.1 on Windows 8 x64 from http://monodevelop.com/Download . When I ran Xamarin, it got updated to 4.0.3. I have installed F# bindings. I have created new F# console project. When I run it, it works fine. When I set a break-point and run it, I get the following error.
System.Runtime.InteropServices.COMException (0x80070032): The request is not supported. (Exception from HRESULT: 0x80070032) at Microsoft.Samples.Debugging.CorDebug.NativeApi.ICorDebug.CreateProcess(String lpApplicationName, String lpCommandLine, SECURITY_ATTRIBUTES lpProcessAttributes, SECURITY_ATTRIBUTES lpThreadAttributes, Int32 bInheritHandles, UInt32 dwCreationFlags, IntPtr lpEnvironment, String lpCurrentDirectory, STARTUPINFO lpStartupInfo, PROCESS_INFORMATION lpProcessInformation, CorDebugCreateProcessFlags debuggingFlags, ICorDebugProcess& ppProcess) at Microsoft.Samples.Debugging.CorDebug.CorDebugger.CreateProcess(String applicationName, String commandLine, SECURITY_ATTRIBUTES processAttributes, SECURITY_ATTRIBUTES threadAttributes, Boolean inheritHandles, Int32 creationFlags, IntPtr environment, String currentDirectory, STARTUPINFO startupInfo, PROCESS_INFORMATION& processInformation, CorDebugCreateProcessFlags debuggingFlags) at Microsoft.Samples.Debugging.CorDebug.CorDebugger.CreateProcess(String applicationName, String commandLine, String currentDirectory, IDictionary`2 environment, Int32 flags) at MonoDevelop.Debugger.Win32.CorDebuggerSession.OnRun(DebuggerStartInfo startInfo) at Mono.Debugging.Client.DebuggerSession.<>c_DisplayClassc.b_a()
The debugger backend for Win32 doesn't work with the 64bit .NET runtime, it only works with the 32bit .NET runtime (and even then, it's known to be broken in various ways).
Can you try installing the Mono runtime and debugging against that runtime instead of the Windows .NET runtime? The Mono Soft Debugger backend is much better and is currently the only debugger backend that is maintained.
To set the Mono runtime as the target runtime, a menu should appear in the "Project" menu (I think) that will allow you to select the Mono runtime.
*** This bug has been marked as a duplicate of bug 11304 ***
You could also try changing the build target to "Debug | x86"