The complete nucleotide sequence of the genome from two yellow fever (YF) virus strains, 1700 and 170-213 was determined. Comparison of these sequences with those of other YF viruses, including the parental virulent Asihi strain, allowed the identification of 48 nucleotide sequence differences which are I70 strain-specific and potentially related to viral attenuation. Another 43 nucleotide sequence differences were not common to all 170 substrains and are therefore substrain specific. Of the 21 changes between 1700 and Asibi 1.5 only five led to amino acid substitutions whereas 13 substrain differences common to all 170-204 substrains produced six amino acid substitutions. Since the exact passage histories of these viruses is known it was possible to calculate, for each strain, the number of accumulated changes per passage. Based on these data the 1700 strain was the most genetically stable virus. 0 I998 Elsevier Science Ltd. All rights reserved.