Bacterial invasiveness and immunological responses were studied in germfree (GF) and conventional (CV) mice infected with Salmonella typhimurium. Bacterial counts of homogenates prepared from liver and spleen showed that the colony forming units (CFU) increased rapidly in GF mice and reached lethal proportions (10(9) cell per organ) by day 6. In CV mice, these counts increased to about 10(4.5) log cell per organ by day 6 and then declined slowly. An increase in serotype-specific IgM and IgG levels was noted in CV mice with a maximum by day 2. Very low values of these IgM and IgG were observed in GF mice during the course of infection. Delayed type hypersensitivity (DTH) response as measured by footpad swelling was higher in CV animals. Higher hypersensitivity to LPS during infection in GF animals resulted in death of all the animals tested for DTH after day 2. The data obtained suggest that during a rapid invasive bacterial infection, the slow development of immune response of GF mice may result in death of these animals.