Lymph node cells were obtained from BCG-sensitized guinea pigs and cultured without (C) and with (Ag) PPD challenge. The dialyzed lymphocyte (LC) supernatants were added to the medium of monolayer cultures of embryonic rat fibroblasts. They were assayed at different cell densities and in the presence and absence of serum. The following results were obtained: Glucose consumption was increased but the cell counts were reduced with both the types of LC supernatants, suggesting a cytotoxic effect. Small increases of cell counts were observed with Ag supernatant in high density fibroblasts in absence of serum. Glycosaminoglycan levels per cell in medium and monolayer were similarly enhanced by both the types of supernatants in presence of serum. As an exception, Ag supernatant reduced cell glycosaminoglycans (GAG) at low cell density. In the absence of serum at low cell density, the increase of medium and cell GAG was markedly higher with Ag supernatant. The GAG pattern of the fibroblast media was scarcely influenced by LC supernatants. In the cell monolayer, however, interesting changes have been observed. Increases of HS and DS were produced by C-supernatant in low density fibroblasts as well as by C- and Ag-supernatants in high density fibroblasts with serum. HS was also increased by C- and Ag-supernatants in serum-free low density fibroblasts. Increases of HA and CS were produced by Ag supernatant in low density fibroblasts with serum. The possible significance of these changes is discussed with regard to chronic inflammation.