When hamsters were infected with Treponema pallidum subspecies endemicum, the composition and activity of the cellular immune components were markedly altered compared to those of sham-infected controls. A population of suppressor T cells (Ts) developed that diminished the ability of the macrophage (M phi) to perform C3b receptor-mediated ingestion (C3bMI) of erythrocytes coated with antibody and complement. Using cyclophosphamide (CY) we examined node and peritoneal cells to determine their role in regulating M phi activity during this infection. In vitro the node and peritoneal T cells from treponemal-infected/CY-treated animals showed considerably less suppressive activity than treponemal-infected/untreated T cells when co-cultured with M phi from infected animals. This response was greater with node T cells compared to peritoneal T cells. Moreover, a quantitative analysis of the mononuclear leucocyte populations from each of these regions showed that CY-treated/uninfected animals had a decreased percentage of node T cells. Despite this reduction of node T cells, peritoneal T-cell populations were only minimally reduced. However, treponemal-infected hamsters concomitantly treated with CY had a significant reduction in the T-cell percentages in both compartments. These results imply that, during this infection, most Ts generated in the node remain there although some are dispersed to supplementary regions. Thus, the development of a suppressor system that effects M phi function may be one way in which treponemes escape total elimination by the host.