Contrary to what has been reported of thymus-independent antigens, we recently demonstrated that trinitrophenylated lipopolysaccharide (TNP-LPS), a class 1 thymus-independent antigen, elicited an anti-TNP anamnestic response in C57BL/6 mice. The question of whether or not class 2 thymus-independent antigens (DNP-Ficoll and DNP-dextran) could also induce immunological memory in this mouse strain was examined. Evidence induce immunological memory in this mouse strain was examined. Evidence is presented that priming with either of these class 2 thymus-independent antigens resulted in the induction of memory B lymphocytes. However, while the memory cells generated by these two antigens were able to be activated by TNP-LPS, they were not triggered by class 2 thymus-independent antigens. Genetic analysis of the capacity of different mouse strains to mount a secondary response to TNP-LPS revealed that major histo-compatibility-associated genes did not play an essential role, but that IgH-V or closely linked gene(s) controlled the immunological memory to TNP-LPS. These findings are discussed in terms of regulatory phenomena which govern the expression of memory response to thymus-independent antigens.