Previous studies have demonstrated the presence of grass pollen-specific T cells in grass pollen-allergic patients (GPA) as well as nonallergic subjects (NA). In order to elucidate a possible seasonal variation in proliferation and cytokine production of peripheral blood mononuclear cells (PBMC), PBMC from 13 GPA and II NA were stimulated with extracts of Phleum pratense and tetanus toroid before and during two grass pollen seasons. IL-4, IL-5 and interferon-gamma were determined by ELISAs. PBMC from GPA demonstrated a decreased proliferative response to grass pollen allergens during the pollen season as compared to NA (p < 0.05), but no difference was found in the response to tetanus toroid. Cells from GPA produced higher amounts of IL-4 and IL-5 than NA (p < 0.05) and the seasonal variation in GPA proliferation was paralleled by the grass pollen-induced production of both IL-4 and IL-5 (p < 0.05), We conclude that during the grass pollen season PBMC from GPA have a reduced ability to proliferate and to produce Th2-type cytokines, This may be due to seasonal migration of the grass pollen-specific T cells from the blood to the tissues of primary allergen exposure.