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In animals, disease progression can be influenced by genetics, environment, management practices, and the type of pathogen. Infection with porcine circovirus 2 (PCV2) causes development of diseases known as porcine circovirus 2-associated diseases (PCVAD), for which there is currently no treatment. In Trial 1, weanling unvaccinated barrows and gilts (n = 229) from two genetic lines were bled at d14, 49, and at necropsy to assess disease progression from natural infection using antibodies (ELISA) and viral copy counts (quantitative PCR). Virus was isolated from infected pigs and sequenced to determine the strain responsible for infection. At d49, 113 animals had active infection. At necropsy, clinical signs of infection were found in 16% of the pigs. In Trial 2, barrows from two genetic lines (n = 81) were infected with an inoculate known to cause PCVAD. Blood and weights were collected before infection and at d7, 14, 21, and 28 to characterize response. Pigs were classified as early responders (n = 33), late responders (n = 40), and non-responders (n = 7) based on IgM levels. Other traits were fitted to a mixed model with effects of group and line, and random effect of litter. Means of viral load throughout the 28-day period differed (P < 0.01) between early and late responders and non-responders. Viremia differed among groups (P < 0.01) at d14, 21, and 28. Viremia of non-responders was 18% less than early and late responders at d14, and 22% less at d21. Non-responders tended to have greater growth rate than the other groups. Variation in immune response can be utilized in genomics studies to identify genetic markers for disease resistance that can be used to select for disease resistance.