Human allergen-induced rhinitis is associated with recruitment and activation of CD4+ T lymphocytes and eosinophils. RANTES is a novel CC chemokine that is a potent chemoattractant for both memory T cells and eosinophils. We therefore investigated RANTES in the nasal mucosa after local allergen provocation. Nasal lavage was performed, and biopsies from the inferior nasal turbinate were taken from 14 atopic, seasonal rhinitic patients and seven normal subjects for as long as 6 h after challenge with a grass pollen extract and after a control (allergen diluent) challenge. In five of seven rhinitics tested, radioimmunoassay of nasal fluid demonstrated increases in RANTES at 2 to 4 h (p < 0.05). Nasal allergen challenge provoked significant increases in RANTES mRNA (p = 0.0015) and protein (p = 0.01) containing cells in the nasal submucosa at 6 h. No changes were observed in normal subjects. Increases in RANTES mRNA+ cells correlated with the associated increases in eosinophils (r = 0.78, p = 0.001). Colocalization studies revealed that the majority of RANTES mRNA+ cells were macrophages (51%) followed by eosinophils (15%), T lymphocytes (11%), and mast cells (3%). Our results demonstrate that allergen-induced rhinitis is associated with release of RANTES and upregulation of RANTES mRNA and protein+ cells, predominantly macrophages, in the nasal mucosa. RANTES synthesis, release, or receptor antagonism may represent a potential target for antiallergy treatment.