Defensins and chemokines are an essential part of the immune response mechanisms in the head and neck mucosa. This work investigates their correlation and their expression pattern in tonsillar disease. Forty-four tonsil tissue samples were obtained from patients who underwent tonsillectomy between 1998 and 1999 for chronic tonsillitis with (n =9) and without (n =25) inflammatory infiltrates and hyperplasia of the tonsil (n =10). Defensin (hBD-1, hBD-2, HNP-1 and HNP-4) and chemokine (RANTES, eotaxin, eotaxin-2, MCP-3, MCP-4 and IL-8) mRNA expressions were analyzed by SQRT-PCR. HNP-4 and eotaxin-2 expressions were positively correlated (P <0.05) in the acute tonsillitis group. HBD-2 and MCP-3 expressions were positively correlated in the hyperplastic tonsils group. Within all groups together, HNP-4 and RANTES expressions were highly positively correlated (P <0.01), and HNP-1 and hBD-2 were positively correlated with IL-8 expressions. Immunohistochemistry demonstrated eotaxin-1 as well as IL-8 production to be predominantly located within the lymphoid follicles and submucosa. RANTES production was shown in the epithelial lining and perivascular tissue. The expression of hBD-1 and hBD-2 was limited to the epithelial lining. Our data support an association between the innate and acquired immune systems on the defensin-chemokine level. The finding of positively correlated hBD-2 and IL-8 expression is biologically relevant because of the proximity of hBD-2 (epithelium) and IL-8 (submucosa) release, as well as the synergistic support of the Th1 system. In addition, our data suggest RANTES as a first-line mediator of perivascular leukocyte recruitment.