Gamma-delta-T cell receptor-positive cells (gamma-delta T cells) have recently been implicated to play a role in the protection against infectious pathogens. Serial studies on gamma-delta-T cells in 14 patients with salmonella infection have revealed that the proportions of gamma-delta-T cells (mean+/-SD: 17.9+/-13.2%) in salmonella infection were significantly increased (P < 0.01) compared with 35 normal controls (5.0+/-2.6%) and 13 patients with other bacterial infections (4.0+/-1.4%). Expansion of gamma-delta T cells was more prominent in the systemic form (28.9+/-10.8%) than in the gastroenteritis form (10.5+/-7.9%) of salmonella infection (P < 0.01). Most in vivo-expanded gamma-delta T cells expressed V-gamma-9 gene product. Increased activated (HLA-DR+) T cells were observed in all the six patients with the systemic form and four of the seven with gastroenteritis form. Especially in the six with systemic form, gamma-delta T cell activation was significantly higher than alpha-delta-T cell activation at the early stage of illness (P < 0.01). When peripheral blood lymphocytes from normal individuals were cultured with live salmonella, gamma-beta T cells were preferentially activated and expanded and most of them expressed V-gamma-9. Purified gamma-delta-T cells also responded to live salmonella in vitro. The present study suggests that human gamma-delta T cells play a role in the protection against salmonella infection in vivo.