Conceived and designed the experiments: RED CER KBE. Performed the experiments: CER. Analyzed the data: CER RED KBE. Wrote the paper: RED CER KBE. Finding and removing highly connected individuals using suboptimal vaccines BACKGROUND: Social networks are often highly skewed, meaning that the vast majority of the population has only few contacts whereas a small minority has a large number of contacts. These highly connected individuals may play an important role in case of an infectious disease outbreak. METHODS: We propose a novel strategy of finding and immunizing highly connected individuals and evaluate this strategy by computer simulations, using a stochastic, individual-and network-based simulation approach. A small random sample of the population is asked to list their acquaintances, and those who are mentioned most frequently are offered vaccination. This intervention is combined with case isolation and contact tracing. RESULTS: Asking only 10% of the population for 10 acquaintances each and vaccinating the most frequently named people strongly diminishes the magnitude of an outbreak which would otherwise have exhausted the available isolation units and gone out of control. It is extremely important to immunize all identified highly connected individuals. Omitting a few of them because of unsuccessful vaccination jeopardizes the overall success, unless non-immunized individuals are taken under surveillance. CONCLUSIONS: The strategy proposed in this paper is particularly successful because it attacks the very point from which the transmission network draws its strength: the highly connected individuals. Current preparedness and containment plans for smallpox and other infectious diseases may benefit from such knowledge. Super-spreader events (cf. [1] ) crucially influence the course of infectious disease outbreaks, as has been shown for SARS, measles and smallpox. Targeting control efforts on individuals with highest potential to spread disease is more effective than mass control [1] . This is very important for diseases like smallpox for which herd immunity is decreasing and stockpiled vaccines are of low eligibility or uncertain immunogenicity [2] [3] [4] [5] [6] . Specific information on social networks and on their contact structures is still scarce, but common properties have been revealed for many networks [7] : it has been shown that the degree distribution of social networks are frequently highly skewed, i.e. they are bound together by just a few very highly connected individuals. The frequency of contacts in such networks is not Poisson distributed (as would be expected in networks which originate from a random mixing process), but follows a skewed and long-tailed distribution [8] : the vast majority of the population has rather few contacts whereas a small minority has a huge number of contacts. Highly skewed networks are ubiquitous in nature and it seems that this particular topology confers "dynamical robustness and reliability to perform a certain function in the presence of perturbations" [9] .