The aim of this study was to examine the levels of gamma interferon (IFN-␥)-, interleukin 4 (IL-4)-, and IL-8-producing cells in peripheral blood mononuclear cells from mink infected with the Aleutian mink disease parvovirus (ADV). As expected, ADV-infected mink developed high plasma gamma globulin values (hypergammaglobulinemia) and enhanced quantities of CD8-positive (CD8؉ ) cells in the blood during the infection. We quantified the percentages of IFN-␥-and IL-4-positive lymphocytes and IL-8-positive monocytes up to week 38 after virus challenge. The results clearly indicated marked increases in the percentages of IFN-␥-and IL-4-producing lymphocytes during ADV infection. The total number of IL-8-producing monocytes in the blood of ADV-infected mink stayed fairly constant during the infection. In order to characterize the phenotype of the cytokine-producing cells, we performed double-labeling fluorescence-activated cell sorter (FACS) experiments with CD8 surface labeling in one channel and cytokine intracellular staining in the other. We found that most IFN-␥ and IL-4 in ADV-infected mink was produced by CD8؉ cells, while in the uninfected mink, these cytokines were primarily produced by a cell type that was not CD8 (possibly CD4-positive cells). We also observed that IL-8 was almost exclusively produced by monocytes. All of the above findings led us to conclude that both Th1-and Th2-driven immune functions are found in mink plasmacytosis.Aleutian mink disease (AD), also known as mink plasmacytosis, is a common and economically important disease in mink. It is caused by a persistent infection with Aleutian mink disease virus (ADV), a nondefective parvovirus (16). In newborn mink, ADV infection may cause atypical interstitial pneumonia (10). This was observed just 20 years ago (34). The classical (adult) form of AD was described in 1956 by Hartsough and Gorham (30), and the disease is characterized by development of hypergammaglobulinemia (plasmacytosis), elevated levels of CD8-positive (CD8 ϩ ) lymphocytes, viral persistency, and immune complex formation (1,2,15,44). The most common pathological findings are glomerulonephritis and arteritis, and severely affected mink often die of renal failure (44). ADV cannot be neutralized in vivo despite the presence of very high concentrations in serum of antibody to virus capsid proteins (8,45). In fact, antibody-mediated enhancement of infection has been observed in connection with ADV infection (3,14,15,32,43). With regard to the identity of the in vivo ADV replicating cell(s) it is generally agreed that the virus-permissive cells probably are Fc receptor-positive cells (7,11,15,32).There is only one existing report on cytokine levels during ADV infection (15). Using reverse transcription-PCR technology, this study reported higher interleukin 6 (IL-6) mRNA levels in lymph nodes from ADV-infected mink (10 and 60 days after infection) than from uninfected mink. It also found biologically active IL-6 in supernatants from short-term lymph node cultures from ADV-infected mi...