Tcrb and Tcrg gene polymorphism was investigated in high (H) and low (L) responder Biozzi mice from selection I, II, and GS by Southern blot analysis with appropriate V and C probes. No polymorphism of the Tcrb haplotype was detected between H and L mice in all selections which were all found to be of the BALB/c type. The H-I and H-II g genotype was of BALB/c and DBA/2 type, respectively. In contrast, a new Tcrg haplotype shared by L-I and L-II mice was identified and characterized by C gamma 1, 2, 3, C gamma 4, V gamma 1, 2, 3, V gamma 5, and V gamma 6 restriction fragment length polymorphisms (RFLPs). Tcrg genotypes were not fixed in the GS selection and two additional new haplotypes were identified in two L-GS mice. An attempt was made to correlate the L-I g genotype with the low responder status by analyzing g haplotypes among highest and lowest responder (H-I X L-I)F2 hybrids immunized with sheep red blood cells (SRBC). No correlation was found in this segregation study, whereas a highly significant one was established with the H-2 haplotype, a locus already known to participate in the genetic control of H-I/L-I difference. The lack of correlation between SRBC response and the Tcrg genotype was consistent with the heterogenous g haplotypes found in mice of the GS selection. Together, the present results suggest that H and L mice have the same Tcrab potential repertoire and that T-cell receptor (Tcr) genes cannot be considered as immune response genes in this model. Our results also indicate that the F2 segregation analysis, given a polymorphic gene, is suitable for an investigation of its immune response functions.