Spatio-temporal factors strongly influence the population dynamics of animals; thus there have been calls to integrate these factors in environmental impact assessment of toxic compounds. To date, methodological difficulties have probably prevented this union. However, new modeling techniques that could help are available. This paper presents the construction and application of an agent-based simulation model of skylarks in agricultural landscapes and its use to assess the impact of pesticides relative to changes in landscape structure and mortality assumptions. Simulations indicated that pesticides had a negative impact on skylark population size. The annual reduction in numbers was variable and depended primarily upon migration mortality and an interaction between weather and pesticides. Altering landscape structure, crop diversity, or migration mortality assumptions resulted in a population change of approximately 37%, compared to a mean of 4% for pesticides. It was concluded that factors other than pesticides are likely to be limiting skylark numbers in most landscapes. This study demonstrates the importance of modeling the interactions between spatio-temporal environmental factors and the study organisms. Agent-based models (ABMs) are able to extract these relationships as emergent properties of their mechanistic nature. Therefore, we recommend the use of ABM models in future regulatory assessment of pesticides.