Here we describe the protocols to perform PFGE analysis of chromosomal DNA from the bacterial species Streptococcus pyogenes (group A streptococcus, GAS) after digestion with the restriction enzyme SmaI. Large parts of the procedures are suitable for application to DNA digested with other restriction enzymes as well. We have put an effort to present extensions to solve possible limitations to the discriminatory power of the method in the specific case of S. pyogenes.