Presence of IFN-γ during priming determines responsiveness to IL-12. CD4+ TG T cells were primed with peptide, APC, IL-2, and either anti-IL-4 and IL-12 or anti-IL-4, anti-IL-12, and anti-IFN-γ (TH1 cells), or with IL-4 and either anti-IL-12 and IFN-γ or anti-IL-12 and anti-IFN-γ (TH2 cells). A portion of the cells were immediately challenged with or without IL-12; extracts were prepared, and STAT-4 binding to FcγRI GAS oligonucleotide sequence was determined as a measure of STAT-4 activation. The cells were also challenged with peptide, APC, and IL-2 (for IL-4 production) or with peptide, APC, IL-2, and either anti-IL-12 or IL-12 (for IFN-γ production).