A key aim in epidemiology is to understand how pathogens spread within their host populations. Central to this is an elucidation of a pathogen's transmission dynamics. Mathematical models have generally assumed that either contact rate between hosts is linearly related to host density (density-dependent) or that contact rate is independent of density (frequency-dependent), but attempts to confirm either these or alternative transmission functions have been rare. Here, we fit infection equations to 6 years of data on cowpox virus infection (a zoonotic pathogen) for 4 natural populations to investigate which of these transmission functions is best supported by the data. We utilize a simple reformulation of the traditional transmission equations that greatly aids the estimation of the relationship between density and host contact rate. Our results provide support for an infection rate that is a saturating function of host density. Moreover, we find strong support for seasonality in both the transmission coefficient and the relationship between host contact rate and host density, probably reflecting seasonal variations in social behavior and/or host susceptibility to infection. We find, too, that the identification of an appropriate loss term is a key component in inferring the transmission mechanism. Our study illustrates how time series data of the hostpathogen dynamics, especially of the number of susceptible individuals, can greatly facilitate the fitting of mechanistic disease models.cowpox ͉ disease ͉ population cycles ͉ Markov chain Monte Carlo T he seminal studies of Anderson and May (1, 2) introduced a framework for modeling the dynamics of pathogens and their hosts that has since underpinned most predictive models of host-pathogen dynamics. It has been standard practice when modeling the dynamics of host-microparasite interactions (viral and bacterial infections) to represent the rate of change of infected hosts I(t) at time t by dI͑t͒ dt ϭ transmission rate ͑infection͒ Ϫ loss rate ͑death ϩ recovery͒.[1]However, empirically based identification of appropriate functional forms for the ''transmission rate'' and ''loss rate'' terms has not generally been possible for systems with host dynamics because of a lack of sufficient data (although refs. 3 and 4 have recently done this for infectious diseases of human populations).To date, most studies have used transmission rate terms that are either density-dependent or frequency-dependent (5, 6). The underlying difference between these is the assumption about how host contact rate c, varies with host density [(N(t))/A], where N(t) is host abundance and A, the area occupied by the population, is usually assumed constant and omitted from the equations (6). For density-dependent transmission, host contact rate varies linearly with density [typically adopted for directly transmitted diseases such as measles (7) and foot and mouth disease (8)], whereas for frequencydependent transmission it is constant [typically adopted for sexually transmitted diseases such as HIV in ...