Hodgkin lymphoma (HL) is characterized by a minority of neoplastic cells, the so-called Reed-Sternberg (RS) cells and a vast majority of reactive cells. RS cells produce chemokines that can attract subsets of peripheral blood cells into HL tissues. To gain insight in the chemokines involved in HL, 16 chemokines were selected based on their ability to recruit different subsets of cells. Five HL, 5 non-HL-derived cell lines, 22 HL, 5 non-HL and 3 control tissues were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Products for 13 of these 16 chemokines were detected in 1 or more of the cell lines tested. No or only very faint signals were obtained in HL for CXCL12, CCL7 and CCL8, but CXCL10, CCL5, CCL13, CCL17 and CCL22 were highly or differentially expressed in HL cell lines and tissues. Immunohistochemistry was performed with antibodies reactive with the latter 5 chemokines on paraffin sections of 21 cases of HL. CCL17 and CCL22 had the highest signals in RS cells at gene expression and at protein levels. CCL17 was specific for the classic HL subtypes, whereas CCL22 also had low signals in NLP samples, as well as in some non-HL. CXCL10 was expressed in a large proportion of HL cases with a predominant expression in EBV-positive cases. The results indicate that RS cells produce a complex pattern of chemokines that are involved in the recruitment of reactive cells and contribute to the paradox of an extensive but ineffective host immune response. © 2002 Wiley-Liss, Inc.