Since late fall of 2004, we have observed the emergence of new respiratory, digestive, hemolymphatic, vascular, and renal lesions associated with Porcine circovirus-2 (PCV-2) infection in pigs in Ontario. These lesions were seen in late nursery, grower, and finisher pigs, 2–3 wk after placement. Affected pigs had a rasping cough, diarrhea, or both. Pigs were often in poor body condition and had generalized lymphadenopathy. At necropsy, many pigs with respiratory signs had prominent pulmonary interlobular edema. Histologically, interlobular septa were widely expanded by edema and alveoli were flooded by proteinaceous edema fluid. Lymphohistiocytic bronchointerstitial pneumonia was present, with mild peribronchial and perivascular lymphohistiocytic cuffing, although infiltration of mononuclear inflammatory cells into alveolar septa was generally much less pronounced than in previous PCV-2 cases. Acute lymphoid necrosis was frequently present in spleen and tonsil from multiple pigs. Immunohistochemical (IHC) staining, using rabbit polyclonal anti-PCV-2 antiserum, identified heavier PCV-2 antigen loads in these more recent cases than we had seen prior to the fall of 2004. Although present in the majority of cases, laboratory tests did not consistently identify the presence of other pulmonary pathogens, such as Streptococcus suis,