Rationale: Hypersensitivity pneumonitis (HP) exhibits a diverse outcome. Patients with acute/subacute HP usually improve while chronic patients often evolve to fibrosis. However, the mechanisms underlying this difference are unknown. Objective: To examine the T-cell profile from subacute (Sub-HP) and chronic (Chr-HP) patients. Methods: T-cells were obtained from bronchoalveolar lavage (BAL) from 25 Sub-HP patients, 30 Chr-HP patients and 8 controls. T-cells phenotype and functional profile were evaluated by flow citometry, cytometric bead array, and immunohistochemistry. Results: Chr-HP patients showed higher CD4⁺/CD8⁺ ratio (median: 3.05, (0.3-15); subacute, median: 1.3 (0.1-10); controls, median: 1.3 (0.7-2.0); p<0.01), and a decrease of T-cells (median: 2.0 (0.5-3.4); Sub-HP: median: 10 (4.8-17); controls: median: 15 (5-19); p<0.01). Chr-HP patients exhibited an increase in the terminally differentiated memory CD4⁺ and CD8⁺ T-cells subsets compared with Sub-HP patients (p<0.05). However, memory cells from Chr-HP showed lower IFN- production, and decreased cytotoxic activity by CD8⁺ T-lymphocytes. Chr-HP displayed a Th2-like phenotype with increased CXCR4 expression [median: 6% (1.7-36) versus controls: median 0.7% (0.2-1.4) and subacute: median: 2.2% (0.1-5.3; p<0.01), and decreased CXCR3 expression (median 4.3% (1.4-25) versus median: 37% (4.9-78) from Sub-HP; p<0.01). Likewise, supernatants from antigen-specific stimulated cells from chr-HP produced higher levels of IL-4 (80±63 pg/ml versus 25±7 pg/ml p<0.01), and lower levels of IFN- (3818±1671 pg/ml vs 100±61 pg/ml; p<0.01) compared with Sub-HP. Conclusions: Our findings indicate that chronic HP patients lose effector T-cell function and exhibit skewing towards Th2 activity, which may be implicated in the fibrotic response that characterize this clinical form.