The nature of cell surface determinants detected by Qa-1-specific alloantisera and cytotoxic T lymphocytes (CTL) in mice of the H-2(f), Qa-1(d) genotype was investigated. The H-2(f), Qa-1(d) strains A.CA and B10.M express both Qa-1(a) and Qa-1(b) encoded alloantigenic determinants (Qa-1.1 and Qa-1.2, respectively), as defined in the prototypic A (or B6-Tla(a)) and C57BL/6 (or A-Tla(b)) strains, respectively. Both anti-Qa-1.1 and -Qa-1.2 sera immunoprecipitate 46K m.w. glycoproteins from H-2(f), Qa-1(d) strains. In addition to 46K m.w. proteins, anti-Qa-1.1 sera, but not anti-Qa-1.2 sera, precipitate 55 to 75K m.w. proteins; the nature of these proteins and their relationship to Qa-1 is unclear at present. Sequential immunoprecipitation experiments and the analysis of several recombinant strains revealed that anti-Qa-1.1 sera also cross-react with a 46K m.w. H-2(f)-encoded alloantigen, probably H-2K(f). Both Qa-1.1 and the non-Qa-1.1 cross-reacting determinants were detected by polyclonal anti-Qa-1(a) CTL on the Qa-1(d) strains. The Qa-1(a) encoded but not the cross-reacting determinants were detected by a cloned anti-Qa-1(a) CTL line. Sequential immunoprecipitation experiments on the recombinant strains B6.AC2 and B10.M(17R), which are Qa-1(d) but not H-2K(f), revealed that the Qa-1.1 and Qa-1.2 determinants do not reside on the same molecule. Furthermore, although Qa-1(b)-encoded determinants were detected on these strains with antisera and with bulk CTL cultures, cloned anti-Qa-1(b) CTL lines thus far analyzed have failed to react with Qa-1(d) targets, indicating that some but not all of the prototypic Qa-1(b)-encoded determinants are expressed by the Qa-1(d) strains.