Insulin 1 nM 156 *Activity of b-PGG was arbitrarily assigned as 100. Transmissibility of the Influenza Virus in the 1918 Pandemic BACKGROUND: With a heightened increase in concern for an influenza pandemic we sought to better understand the 1918 Influenza pandemic, the most devastating epidemic of the previous century. METHODOLOGY/PRINCIPAL FINDINGS: We use data from several communities in Maryland, USA as well as two ships that experienced well-documented outbreaks of influenza in 1918. Using a likelihood-based method and a nonparametric method, we estimate the serial interval and reproductive number throughout the course of each outbreak. This analysis shows the basic reproductive number to be slightly lower in the Maryland communities (between 1.34 and 3.21) than for the enclosed populations on the ships (R(0) = 4.97, SE = 3.31). Additionally the effective reproductive number declined to sub epidemic levels more quickly on the ships (within around 10 days) than in the communities (within 30–40 days). The mean serial interval for the ships was consistent (3.33, SE = 5.96 and 3.81, SE = 3.69), while the serial intervals in the communities varied substantially (between 2.83, SE = 0.53 and 8.28, SE = 951.95). CONCLUSIONS/SIGNIFICANCE: These results illustrate the importance of considering the population dynamics when making statements about the epidemiological parameters of Influenza. The methods that we employ for estimation of the reproductive numbers and the serial interval can be easily replicated in other populations and with other diseases. The emergence of the highly pathogenic avian influenza strain H5N1 has raised concerns of an imminent influenza pandemic. Public health workers, government officials and disaster planners have an increasing interest in better understanding the potential impact of an influenza pandemic and possible strategies for containment. Crucial in this planning is an understanding of the basic epidemiology of the disease in various settings. This has led to a growing interest in the analysis and understanding of past epidemics, particularly that of 1918, the most virulent and deadly influenza epidemic of the 20th century. Mortality has been estimated at 50-100 million people worldwide as a result of influenza in the 1918 pandemic [1] . It is reasonable to suppose that by better understanding the transmission dynamics of the highly pathogenic virus in 1918, we can gain greater insight into the dynamics, and thus potential methods of control, for a future pandemic [2] . Important parameters for understanding disease transmission are the reproductive number and the serial interval [3] . The basic reproductive number is defined as the average number of secondary infections created from a primary infection in an entirely susceptible population [4, see also 5] . A more complex, but perhaps meaningful parameter is the effective reproductive number which defines the average number of secondary infections an infected will create at a given point in the epidemic. This parameter takes into account that not all contacts of an infected individual are with susceptible persons, as well as the impact of public health control measures. Control strategies are typically targeted to drive this number below one and maintain it there, as this will lead to eventual extinction of the epidemic. An example of this is herd immunity, or immunity to a disease that is incurred from a sufficiently large proportion of the population being immune to a disease. Modeling techniques are often used to determine the proportion of the population that should be vaccinated in order to have the reproductive number low enough to avoid outbreaks of disease [6] .