Patho-epidemiological studies have shown that thyroid lymphomas (TL) develop in thyroids affected by chronic lymphocytic thyroiditis (CLTH). Cytokines produced in CLTH might play a pivotal role for lymphomagenesis, because previous reports indicate an important role of cytokines in lymphomagenesis. We examined the expression of interleukin-7 (IL-7), a pleiotropic cytokine that acts mainly on cells of the hematolymphoid system, and IL-7 receptor (IL-7R) in both TL and CLTH by RT-PCR. IL-7-specific transcripts were detected more frequently in TL than in CLTH lesions (p < 0.01). IL-7 expression was higher in TL than in CLTH. IL-7R and the common gamma chain were expressed in all but one TL and in all CLTH lesions, in similar levels. We established the sensitive in situ hybridization (ISH) method for detection of IL-7. ISH for IL-7 revealed cytoplasmic signals among cells in the germinal center and mantle zone of lymphoid follicles and interfollicular areas in the TL and CLTH lesions. In the lymphomatous areas of TL, similar numbers of scattered large and small lymphoid cells expressing IL-7 were found. The number of IL-7-expressing cells counted in 10 fields in TL (119.4 +/- 10.6 cells) was significantly higher than found in CLTH lesions (43.1 +/- 4.6) (p < 0.001). These findings suggest a pathogenetic role for IL-7 in the development of TL. ISH showed that the germinal center cells, interfollicular cells, and lymphoma cells expressed IL-7R, but mantle zone cells did not. Because lymphoid cells in lymphoid follicles and the interfollicular area formed in CLTH expressed IL-7, TL cells might proliferate via their own IL-7 and IL-7R, and via IL-7 from reactive lymphoid cells.