In October 2000, the Ministries of Health of the Dominican Republic and Haiti notified two cases of acute flaccid paralysis (AFP) in rural areas, one of them in a 9-month-old female, and the other in a 2-year-old female, respectively. Stool samples that were obtained from these cases, which occurred in July and August 2000, after a 9-year interruption of wild poliovirus circulation in the Western Hemisphere, revealed the presence of type 1 poliovirus. Genetic sequencing, which was later performed at the Centers for Disease Control and Prevention, in Atlanta, Georgia, United States of America, revealed an atypical descendant of the virus used in the manufacture of the oral polio vaccine (OPV), but with 3% genetic divergence with respect to the parent strain. Normally, viral isolates that derive from vaccine components show 99.5% genetic agreement with the parent strain; in wild polioviruses, on the other hand, this agreement is usually less than 82.0%. Thus, the 3% genetic divergence detected in this study suggests that, in areas with low vaccine coverage, the virus used in the vaccine remained in circulation for at least two years, during which it recovered the neurovirulence and communicability of wild poliovirus type 1. This report describes the characteristics and results of the active search for cases of AFP that was sparked by the detection of the two index cases. It also looks at the public health implications of this outbreak for the entire Region of the Americas.