Background. The malignant cells in HL comprise only a small fraction of the total tumor population but orchestrate an inflammatory microenvironment of reactive cells that sustains tumor cell survival and growth. HL patients (pts) have high systemic levels of inflammatory cytokines and chemokines and low lymphocyte count (<0.6 x 10^9/L) is a well-established prognostic factor in advanced disease. The aim of this pilot study was to characterize the phenotype of circulating lymphocytes in HL pts. Material and methods. Peripheral blood samples were obtained from 10 HL pts and 12 sex- and age-matched healthy controls. Nine pts had classical HL and 1 had nodular lymphocyte predominance (NLP) HL. Five pts had limited (stage I-IIA) and 5 had advanced (IIB-IV) disease. Pts with ongoing acute EBV infection were excluded. All pts had negative serology for HIV. Absolute numbers of CD19+, CD3+, CD4+, CD8+, NK and NKT cells, functional T helper subpopulations (Th1/Th2/Th17), CD4+ and CD8+ memory cell subsets and expression of CTLA-4, PD-1, CD69 and Ki-67 on CD4+ and CD8+ T cells were assessed by flow-cytometry. Results. HL pts with advanced disease had lower lymphocyte counts compared to controls (median 0.9 vs 1.7 x 10^9/L, p=0.01) while no difference was observed for pts with limited disease. Compared to controls, HL pts had lower CD19+ cell numbers irrespective of disease stage (0.075 vs 0.05 x 10^9/L in pts with limited and advanced disease vs 0.19 x 10^9/L in controls, p=0.009 and p= 0.0003, respectively). Pts with advanced disease had also significantly lower numbers, compared to controls, of CD3+ (median 0.78 vs 1.36 x 10^9/L, p=0.04), CD4+ (median 0.3 vs 0.5 x 10^9/L, p=0.04), Tregs (median 0.008 vs 0.017 x 10^9/L, p=0.004), Th2 (median 0.18 vs 0.28 x 10^9/L, p<0.05) and Th17 cells (median 0.03 vs 0.08 x 10^9/L, p=0.006), while no difference was observed for Th1. HL pts had lower numbers of naive CD8+ cells irrespective of disease stage, while central memory CD4+ cells were lower in advanced disease. No difference was observed with regard either to the numbers of proliferating (Ki67+) or PD-1- and CTLA-4-expressing CD4+ and CD8+ cells. On the other hand, CD69+CD4+ cells were significantly higher in pts with limited disease compared to controls (median 0.04 vs 0.01 x 10^9/L, p=0.04). Conclusions. These observations suggest that the immune microenvironment in HL plays a role that is far from being only local. Further studies are ongoing in larger cohorts of pts.