The antigen specificity of hybridoma antibodies with activity against H-2 antigens was analyzed by testing lymphocytes of inbred lines and their recombinants, as well as B10.W lines and wild mice in relation to the reactivity of alloantisera. Within the limited test panel of 11 inbred strains and their recombinant derivatives, the hybridoma antibodies reacted concordantly to alloantisera with public (H-2.5, H-2.11, and Ia. 13) and private (H-2.23) antigens. However, when tested on cells of B10.W lines or wild mice discordant reactions were observed, indicating that the antigenic determinants recognized by the hybridoma antibodies are included in the antigens defined by alloantisera within the inbred test panel. In wild mouse populations, these determinants do also occur independently of those which comprise the alloantisera-defined specificities. The results point to an even higher complexity of MHC antigens than envisaged so far, and it appears that a certain allele might be defined only by a certain set of antigenic determinants. Because of the discrepant reactions of alloantisera and hybridoma antibodies, it has been proposed that antigenic determinants detected by hybridoma antibodies receive a numerical designation according to their description but independent of antigens defined by alloantisera, even if they match the reactivity pattern of an alloantiserum-defined antigen specificity within the inbred panel.