Treatment of porcine kidney (PK-15) cells with either interferon-gamma (IFN-gamma) or endosomal- lysosomal system acidification inhibitors increases replication of porcine circovirus type 2 (PCV2). In the present study, the effect of a combination of these treatments on the number of infected cells and virus yield was tested. The number of PCV2 (Stoon-1010)-infected PK-15 cells increased in cells treated with ammonium chloride (445 +/- 39% increase), IFN-gamma (446 +/- 8%), ammonium chloride + IFN-gamma (1721 +/- 283%), chloroquine diphosphate (1037 +/- 121%), chloroquine diphosphate + IFN-gamma (2199 +/- 255%), monensin (950 +/- 178%) and monensin + IFN-gamma (1948 +/- 60%). Combined IFN-gamma and endosomal-lysosomal system acidification inhibitors increased PCV2 yield by up to 50 times compared to untreated PK-15. This augmented virus replication in PK-15 cells may be helpful in the production of PCV2 vaccines.