UNLABELLED: Lymphocytes are major players in the development of innate and adaptive immune responses but their behavior in patients with acute stroke has received little attention. EXPERIMENTAL PROCEDURES: Using flow cytometry we identified total lymphocytes, T cells, helper T (Th) cells, cytotoxic T lymphocytes (CTL), natural killer (NK) cells, B cells, and regulatory T (Treg) cells in 46 consecutive patients with acute stroke within a median of 180 min of clinical onset, and at days 2, 7, and 90. Daily neurological score (National Institutes of Health Stroke Scale), diffusion-weighted imaging on brain magnetic resonance imaging, functional impairment, and stroke-associated infection (SAI) at day 7 were assessed. Apoptosis in lymphocyte subsets, tumor necrosis factor (TNF) -alpha/interleukin (IL) -4 production in stimulated Th and CTL, cluster of differentiation 86 (CD86) (B7-2) expression in B cells, cortisol and metanephrine in serum were measured. Multivariate analyses were used to evaluate SAI, and stroke outcome. RESULTS: Increased apoptosis and a fall of T, Th, CTL, B, and Treg cells were observed after stroke. Severer stroke on admission and SAI disclosed a greater decline of T, Th, and CTL cells. Increased cortisol and metanephrine was associated with severe stroke and SAI, and inversely correlated with T, and CTL. T cells, and CTL were correlated with infarct growth. Stroke but not SAI resulted in lower TNF-alpha production in Th cells. SAI showed the greatest fall of lymphocytes, T, Th, and CTL, but not B cells, or Treg. Poor outcome was associated with reduced levels of B cells, and increased expression of CD86 in B cells, but not with SAI. CONCLUSION: Lymphopenia and increased apoptosis of T, Th, CTL, Treg and B cells are early signatures after human stroke. A decreased cellular response after stroke is a marker of ongoing brain damage, the stress response, and a higher risk of infection. A lower humoral response is predictor of poorer long-term outcome.