Within the framework of the Health Protection Agency's programme of enhanced surveillance of Staphylococcus aureus with Panton-Valentine Leucocidin (PVL-SA) in England and Wales conducted during 2005-2006, we identified 720 PVL-SA, representing a two-fold increase between 2005 (n = 224) and 2006 (n = 496). The number of PVL-methicillin-resistant S. aureus rose from 119 to 159 in that period. Isolates were referred by 112 centres and included outbreaks of PVL-related disease in community and healthcare settings. One hundred individuals had systemic disease symptoms. Planned systematic surveillance-based studies aim to better address the question of whether these increases reflect an increasing prevalence of PVL-SA and/or improved case ascertainment of PVL-related syndromes.