Abstract Background Public health surveillance and epidemiologic investigations are critical public health functions for identifying threats to the health of a community. Very little is known about how these functions are conducted at the local level. The purpose of the Epidemiology Networks in Action (EpiNet) Study was to describe the epidemiology and surveillance response to the 2009 pandemic influenza A (H1N1) by city and county health departments in the San Francisco Bay Area in California. The study also documented lessons learned from the response in order to strengthen future public health preparedness and response planning efforts in the region. Methods In order to characterize the epidemiology and surveillance response, we conducted key informant interviews with public health professionals from twelve local health departments in the San Francisco Bay Area. In order to contextualize aspects of organizational response and performance, we recruited two types of key informants: public health professionals who were involved with the epidemiology and surveillance response for each jurisdiction, as well as the health officer or his/her designee responsible for H1N1 response activities. Information about the organization, data sources for situation awareness, decision-making, and issues related to surge capacity, continuity of operations, and sustainability were collected during the key informant interviews. Content and interpretive analyses were conducted using ATLAS.ti software. Results The study found that disease investigations were important in the first months of the pandemic, often requiring additional staff support and sometimes forcing other public health activities to be put on hold. We also found that while the Incident Command System (ICS) was used by all participating agencies to manage the response, the manner in which it was implemented and utilized varied. Each local health department (LHD) in the study collected epidemiologic data from a variety of sources, but only case reports (including hospitalized and fatal cases) and laboratory testing data were used by all organizations. While almost every LHD attempted to collect school absenteeism data, many respondents reported problems in collecting and analyzing these data. Laboratory capacity to test influenza specimens often aided an LHD’s ability to conduct disease investigations and implement control measures, but the ability to test specimens varied across the region and even well-equipped laboratories exceeded their capacity. As a whole, the health jurisdictions in the region communicated regularly about key decision-making (continued on next page) (continued from previous page) related to the response, and prior regional collaboration on pandemic influenza planning helped to prepare the region for the novel H1N1 influenza pandemic. The study did find, however, that many respondents (including the majority of epidemiologists interviewed) desired an increase in regional communication about epidemiology and surveillance issues. Conclusion The study collected information about the epidemiology and surveillance response among LHDs in the San Francisco Bay Area that has implications for public health preparedness and emergency response training, public health best practices, regional public health collaboration, and a perceived need for information sharing.