Toxoplasmosis, caused by Toxoplasma gondii, is one of the most common parasitic infections of humans and other warmblooded animals. It has been found worldwide, and nearly one third of humanity has been exposed to the parasite. In most adults, infection rarely produces severe clinical manifestations; however, there have been recent reports of focal ocular toxoplasmosis in otherwise healthy adults. Congenital infection usually occurs when a woman becomes infected during pregnancy and transmits the pathogen to the fetus. Devastating disease can also result in immunosuppressed patients, such as those given large doses of immunosuppressive agents in preparation for organ transplants or those with acquired immunodeficiency syndrome. In any case, the immunosuppressed host may die from toxoplasmosis unless treated. Humans most commonly become infected through ingestion of tissue cysts in undercooked or uncooked meat, or by ingesting food or water contaminated with sporulated oocysts from infected cat feces. Food animals, such as pigs, become infected by the same routes as humans, resulting in meat products containing tissue cysts, which can infect consumers. Consumption of viable tissue cysts in meat products has been blamed for a significant portion of Toxoplasma gondii infections to humans for decades with little supporting evidence. Our laboratory completed the National Retail Meat Survey (NRMS) for Toxoplasma gondii to determine the risk to U.S. consumers of purchasing meat containing viable T. gondii tissue cysts at the retail meat counter; the study sampled retail grocery outlets servicing 80% of the U.S. population. The NRMS determined that viable T. gondii was present in 0.4% of pork samples, but not in beef or chicken, though 1.5% of chicken samples were seropositive, indicating exposure to T. gondii. The study further determined that the level of viable Toxoplasma present in beef, pork, and chicken, the major meat products consumed in the U.S., could not account for the yearly incidence of Toxoplasma infection that is estimated to occur in the U.S. population. The NRMS was the first study where prevalence of a pathogen in animals was directly linked to consumer risk in the retail meat case, and is a model for risk assessment of pathogens from farm to table. Reduction of risk for human and food animal infection with Toxoplasma gondii has been hampered by the lack of epidemiological data documenting the predominant routes of infection (oocyst vs. tissue cyst consumption) in horizontally transmitted (i.e., non-congenital) toxoplasmosis. Until recently, there were no tests that could differentiate between oocyst ingestion (the stage excreted in cat feces) and tissue cyst ingestion (the stage found in meat) as the infection route. We described previously described an oocyst-specific protein (TgERP), which elicits antibody in T. gondii–infected pigs and humans. The presence of this antibody reliably differentiates infection by oocysts from infection by tissue cysts within 6–8 mo of initial exposure. In this study, we conducted a serological census of oocyst-induced Toxoplasma infection using human sera and demographic data collected during the National Health and Nutrition Examination Survey from 1988-1994 (NHANES III), and 1999-2004 (NHANES). The census utilized all sera previously found to be Toxoplasma positive, but applied in a newly developed ELISA based on the oocyst-specific antigen. The resulting seroprevalence data from acute infections strongly suggests that oocyst-transmitted Toxoplasma accounts for the vast majority of human infections, and that meat borne toxoplasmosis is a minor contributor to human infections in the U.S.