Introduction: Intestinal mucosa represents an important portal of entry of HIV and a site of virus reservoir and active replication. Recently, in HIV patients, an early depletion in intestinal lamina propria T lymphocytes (LPT) has been described. HIV-1 gp 120 has been demonstrated to promote apoptosis in non-infected isolated peripheral blood T cells, therefore we investigated whether gp 120 modulates apoptosis of normal human intestinal lamina propria T cells.Materials and Methods: Purified T cells were obtained by immunomagnetic negative selection from human lamina propria mononuclear cells isolated from surgical specimens by enzymatic procedure. Cells were incubated with or without recombinant gp120 (10 mg/ml) and cultured either in the absence of any stimulus or in the presence of plate-bound anti-CD3 Ab or soluble anti-CD2 Ab (T11 2 + T11 3 ). Apoptosis was assessed by flow cytometric analysis after propidium iodide staining.Results: We observed that preincubation of normal LPT cells with HIV-1 gp120 accelerates the apoptosis observed during CD2-pathway stimulation of LPT cells. This process is mediated by Fas/Fas ligand interaction and related to an increased induction of Fas ligand mRNA by gp120.Conclusion: HIV-1 gp120 could contribute to the depletion of non-infected LPT cells inducing a premature cell death.