In the Mekong delta, backyard pig rearing plays an integral role in recycling nutrients in farming systems and generating valuable cash income. However, development has been hampered by fatal epizootics of piglets and reproductive failure of sows. Diseases are named by symptoms and blindly treated with antibiotics. As antibiotics are often ineffectual, involvement of viral diseases are suspected. To identify the causative agent, we first sero-surveyed porcine reproductive and respiratory syndrome (PRRS) and pseudorabies with 478 sera from non-vaccinated pigs collected from backyard farms, state farms and slaughterhouses in Can Tho province between 1999 and 2002. Antibodies for PRRS were first detected in 2002 in backyard farms and at high prevalence in state farms with increased piglet mortality. A few backyard breeder pigs had antibodies for pseudorabies in 2000 and 2002. With compulsory classical swine fever (CSF) vaccination, we examined the relationship between vaccination and antibodies in 70 serum samples. Seventy-nine percent of vaccinated breeders had CSF antibodies-higher than expected with irregular vaccination. Since circulation of CSF virus was suspected, isolation was attempted at 10 farms with fatal epizootics between 2002 and 2003. The viruses were detected at all farms and clustered within genogroup 2, despite vaccines corresponding to genogroup 1. This study demonstrated virologically/serologically the existence of PRRS, pseudorabies and CSF viruses in the Mekong delta of Vietnam. We also identified CSF as a cause of piglet mortality that disastrously affected backyard farming. Vaccine standardization and proper instructions are needed to simplify diagnosis and complement established simultaneous vaccination of sows with piglets.