We prospectively evaluated 52 consecutive cases of newly identified absolute lymphocytosis to determine the hematologic and immunophenotypic features of transient stress lymphocytosis (TSL). The lymphocytosis in all cases was associated with an acute stressful event and ranged from 4,000 to 10,400/μL (4.0-10.4 × 109/L). Compared with healthy individuals, patients with TSL showed an increase in the total WBC, absolute lymphocyte (ALC), absolute neutrophil (ANC), and platelet counts with no difference in hemoglobin levels. Immunophenotypic analyses of 38 cases revealed increases in absolute numbers of T, B, and natural killer cells. Both CD4+ and CD8+ T cells were increased, predominantly accounted for by an increase in memory cell subsets, with no change in gamma/delta T cells. Follow-up studies showed a significant reduction in the ALC with a concurrent increase in the ANC and reduction in hemoglobin values. The reduction in lymphocytes at resolution was accompanied by reduction in all broad lymphocyte subsets. However, naive and memory subsets showed different patterns of alteration within the CD4+ and CD8+ populations, suggesting that acute stress differentially affects the in vivo distribution of these subsets.