AbstractEvidence is presented that T helper cells change their Lyt‐1,2 phenotype, from Lyt‐1+2−to Lyt‐1−2+, during a secondary response. In a secondary adoptive transfer the Lyt phenotype of carrier‐primed T cells was established before and after secondary challenge using monoclonal antibodies and both positive and negative selection in the fluorescence‐activated cell sorter. In a carrier‐primed donor, the T helper cells were Lyt‐1+2−whereas 3 days after boosting the majority were Lyt‐2+, and resistant to treatment with anti‐Lyt‐1 and complement. Parking experiments in lethally irradiated recipients confirmed that Lyt‐2+T helper cells were generated from Lyt‐2−precursors. In a primary response, both Lyt‐2−and Lyt‐2+T helper cells were present 4 to 20 days after immunization. Therefore T helper cells do not exhibit invariant e