The specificity of the influenza nucleoprotein-induced T-cell proliferative response by mouse strains differing in either H-2- or non-H-2-linked background genes was compared by using a panel of synthetic peptides covering 90% of the nucleoprotein molecule. The results showed, as expected, that H-2 genes strongly influenced the major regions of the molecules recognized by T cells, as the response was focused on different peptides in mice of different H-2 haplotypes. However, some regions of the molecule (e.g. 260-283) were recognized by several different haplotypes, with overlapping but distinct minimal determinants. The lymph node proliferative response appeared to be predominantly restricted by the I-A molecule, as expression of I-E in mice did not result in any detectable recognition of additional epitopes. In the majority of cases the same T-cell epitopes were recognized by mouse strains sharing the same H-2 haplotype but differing in many background genes. Low responsiveness was however observed to p55-77 by DBA/2 and p127-141 by AKR mice to which other H-2d or H-2k strains were high responders. Low responsiveness is therefore unlikely to be a consequence of failure of these peptides to bind to the relevant major histocompatibility complex class II molecule. In addition antigen-presenting cells from the DBA/2 low responder strain was able to process and present whole influenza virus or nucleoprotein as well as antigen-presenting cells from the high responder BALB/c strain. It is therefore suggested that low responsiveness to the peptide p55-77 may be due to a 'hole in the T-cell repertoire', caused perhaps by expression of Mls-1a in the DBA/2 strain. This is supported by the observation that low responsiveness to this epitope appears to be dominant in F1 (low x high) mice.