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The standard response is use MXD Doctor (in Win7: C:\Program Files (x86)\ArcGIS\Desktop10.0\Tools)
If that doesn't work, get well aquanted with F5?
Thanks for the suggestion. I have already tried that but, it did not find any problems, and yes me and the F5 key are very well acquainted.
Can you make a new blank MXD and use the "Change Layout" tool on the Layout View Toolbar to import the layout settings from your messed up mxd and then copy the data frame over? That too has worked for me in the past to get rid of a strange MXD.