Help for a secondary response to a determinant can be dependent on previous exposure to other determinants of the macromolecule; it can also be independent of sensitization to such carrier determinants. A helper effect, which is independent of the hapten carrier bridge, can be seen in the indirect plaque-forming response. This Th-2 type of reactivity was observed in tissue culture with spleen cells from A/J and C57BL/6 mice, immunized with various macromolecules. The spleen cells of these mice were exposed in tissue culture to the sensitizing macromolecule and to antigens conjugated to a macromolecule which was structurally unrelated to the sensitizing macromolecule. Sensitization of the spleen cell donor with the hapten was not required for this help to be given if the hapten was 2,4-dinitrophenyl, but was required when the hapten was p-azobenzene sulfonic acid. The age, at which the Th-2 helper effect was first seen, shows polymorphism. The effect was detected well after sexual maturity, and 50% of the final value was reached only when the animal had passed the 20th week of its life. The variation in age of detectable Th-2 capacity depended on the nature of the hapten; with 2,4-dinitrophenyl, as the hapten, A/J and C57BL/6J differed very little in the age at which the Th-2 capacity became detectable; with p-azobenzene sulfonic acid the Th-2 capacity was detectable at a much later age in A/J than in C57BL/6 mice.