Mice selected by Biozzi for high and low responses to sheep erythrocytes were investigated for resistance to subcutaneous Salmonella typhimurium infection. The resistance was measured by LD50 values, viable bacterial counts in liver and spleen at 10 days, and the kinetics of infection over 4 weeks. High responder mice were susceptible to S. typhimurium injected subcutaneously (LD50 less than 10) and low line resistant (LD50 3 x 10(6)). Control of natural resistance to S. typhimurium in inbred mice is primarily by a single gene. Ity, on chromosome 1. Results with hybrid generations of Biozzi mice with either BALB/c (sensitive) or CBA (resistant) inbred mice indicated additional genetic control of resistance in Biozzi mice. Analysis of resistance data of backcrosses of (high x low)F1 with either parental strain showed this genetic control to be at least one other gene in the Biozzi mice, not linked to Ity. The antibody responses in the hybrid generations and inbred and Biozzi parental strains were tested by haemagglutination assays and ELISA. After specific stimulation of the mice there was an inverse relationship between resistance to S. typhimurium and antibody levels.