Windows 10 
python 3.5
small function in a small module 
contained a string len(str1) == 5000 {approx}
str1 = str1.replace('  ',' ')
did not work
added, via copy & paste, a second identical line
str1 = str1.replace('  ',' ')
str1 = str1.replace('  ',' ')
AND IT WORKED

Could you provide us with a sample file that demonstrates this behaviour?

Please use stackoverflow or python-tutor list to get help on this.
https://mail.python.org/pipermail/tutor/

This is unlikely a problem as you are using replace the send time on new string object.

The .replace() method is not recursive (it only makes one pass through the string), so for example:

>>> example = '   '  # three spaces
>>> example = example.replace('  ', ' ')  # replace two spaces with one space
>>> example  # should be two spaces
'  '  
>>> example = example.replace('  ', ' ')  # replace two spaces with one space
>>> example  # should be one space
' '