The subcellular localization of JAK3 was examined by quantitative image analysis. For the first time, JAK3 was found to be located in the nuclei of primary CD4 lymphocytes. A comparable quantity of JAK3 was recovered in CD4 lymphocytes from healthy donors and HIV-infected patients. By contrast, far more phosphorylated JAK3 (pJAK3) was found in the nuclei of CD4 lymphocytes from HIV-infected patients than from healthy donors. The correlation detected between the quantity of pJAK3 in the nuclei of CD4 lymphocytes and the increase in HLA-DR at their surface suggests that pJAK3 may play a role in the deleterious immune activation characterizing HIV-infected patients.