Germinal centers (GC) primarily consist of B cells along with a small number of T cells (5 to 10%) and follicular dendritic cells (FDC) (≤1%). Although extensive Ag-driven B cell proliferation and maturation occurs in GC, very little is known about the role of cytokines in the development of GC B cells. Therefore, to identify cytokines present in the GC microenvironment that may influence B cell development, we systematically examined cytokine gene expression by GC cells, GCT cells (CD57+/CD4+), GC B cells (CD77-), and FDC (HJ2+) were isolated from human tonsils by cell sorting using a flow cytometer. Freshly isolated GC cells were examined for mRNA expression for IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-α, and IFN-γ using reverse transcription polymerase chain reaction. Freshly isolated GC T cells consistently expressed IL-4 mRNA (11 of 12 tonsils), whereas CD57- Th cells (mostly non-GC Th cells) were often negative for IL-4 mRNA. When the other nine cytokine mRNA were studied, freshly isolated CD57+ Th cells occasionally expressed mRNA for IL-10, TNF-α, and IFN-γ. CD57- Th cells were occasionally positive for IL-1β, IL-10, IFN-γ, and TNF-α, and negative for IL-2 and IL-6. Freshly isolated GC B cells as well as FDC failed to express detectable quantities of mRNA for all 10 cytokines that were studied. Thus, IL-4 is the only cytokine out of 10 that is consistently expressed in GC and may be important for the development of B cells in GC. After stimulation of CD57+ Th cells with PWM, production of IL-4 mRNA was dramatically reduced, whereas CD57+ Th cell production of IL-4 was greatly augmented. This finding indicates that GC T cells may differ from other Th cells in cytokine gene expression and that results of cytokine production obtained after in vitro stimulation do not always reflect in vivo results.