To elucidate the relationship between the virulence of intracellular bacterium and its ability to induce gamma/delta T cells in the host during infection, we examined the differences in appearance of gamma/delta T cells in mice infected with Salmonella choleraesuis virulent strain RF-1 carrying a virulence plasmid of 50 kb, and with avirulent strain 31N-1 cured of the 50-kb plasmid. The number of gamma/delta T cells in the peritoneal cavity was increased to a significant level on day 3 after an intraperitoneal infection with a sublethal dose (5 x 10(4) colony-forming units) of avirulent strain 31N-1. On the other hand, no increase in the number of gamma/delta T cells was evident in the peritoneal cavity at any stage after infections with various doses of virulent strain RF-1, although the numbers of the bacteria were drastically increased. Similar to that seen in the peritoneal cavity, the number of gamma/delta T cells in the liver was significantly increased after an intraperitoneal infection with avirulent strain 31N-1 but not with virulent strain RF-1. The early appearing gamma/delta T cells during salmonellosis with avirulent stain 31N-1, which preferentially used V gamma 1/V delta 6, showed blastogenesis in response to purified protein derivative (PPD) derived from Mycobacterium tuberculosis. The gamma/delta T cells also responded to the peritoneal adherent cells in mice infected with avirulent strain 31N-1 6 d previously, which expressed a high level of endogenous heat-shock protein (hsp) homologous to the mycobacterial 65-kD hsp. The expression of the hsp, however, was not prominent in the adherent cells in mice infected with virulent strain RF-1. These results suggest that the gamma/delta T cells specific for PPD may play important roles in host defense against murine salmonellosis, and that the virulence of Salmonella may be inversely correlated with its ability to induce endogenous hsp in the infected macrophages, which in turn stimulate the gamma/delta T cells in the host during salmonellosis.