T-cell proliferative responses were studied in two villages in Gabon with different levels of Loa loa transmission. The first village (Okoumbi) had an annual transmission potential (ATP) of ≈9,000 infective larvae (L3)/person/year (high transmission village), while the second village (Ndjokaye) had an ATP of ≈1,000 L3/person/year (low transmission village). Proliferation and cytokine assays were performed on peripheral blood mononuclear cells (PBMC) from individuals aged 18 years and over using either mitogens (concanavalin A or phytohemagglutinin), antigens (purified protein derivative [PPD], irrelevant antigen), or soluble extracts of L3, microfilariae, or adult L. loa. PBMC from individuals in the low transmission village responded better to stimulation with adult antigen and to PPD than did PBMC from individuals in the high transmission village (P = 0.0031 and P = 0.0012, respectively). These data suggest that high levels of transmission of L. loa depress both specific and nonspecific T-cell proliferative responses in infected humans.