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Genetic and environmental effects on incidence of Porcine Circovirus Associated Disease (PCVAD) and immune responses to Porcine Circovirus 2 (PCV2), and their relationships with body weights were studied in 3,440 pigs of the Nebraska litter size selection lines. Pigs were weighed at birth, weaning, 65, and 180 days of age and scored for symptoms of PCVAD every 10 days from 70 to 180 days of age. Necropsies were performed to confirm accuracy of scoring. PCV2 viremia, and anti bodies to PCV2, Porcine Reproductive and Respiratory Syndrome Virus, Myco plasma hyopneumoniae and Actino bacillus pleuropneumoniae were measured in serum from blood samples drawn at various ages from live pigs and in tissues of pigs necropsied. PCV2b genotype was confirmed to be the pathogen causing PCVAD; other pathogens studied were not involved. Pigs with no symptoms of PCVAD had significantly greater weights (0.22, 1.12, 6.6, and 46.0 lb, at birth, weaning, 60 d, and 180 d, respectively) than affected pigs. Heritability of PCVAD score was 16% + 4%. The location in which pigs were raised accounted for 22% of the variation in PCVAD score. Nearly all pigs were non-viremic until 90 days of age, but many had antibody titers at weaning and at 60 days of age. These maternal antibodies appeared to protect pigs from PCVAD until approximately 90 days of age. Heritability of viremia level at 90 days of age was greater than at 125 days of age (38 ± 11% vs 11 ± 8%). Genetic variation existed for antibody titers at 90 (h2 = 55 ± 21%) and 125 days of age (h2 = 10 ± 8%). Incidence of PCVAD was correlated genetically with body weights, PCV2 viremia level, PCV2 antibody titers, and body weights. Expected response to direct selection for reduced PCVAD score was very low (-0.89% in one generation), whereas expected response to index selection for 65-day weight and PCV2 viremia and antibody titers at 90 days of age was -8.0%, 998% greater than direct selection. Genomic selection for decreased incidence of PCVAD is feasible.