A chimeric macaque/human (PRIMATIZED®) anti-CD23 antibody, p6G5G1, demonstrated a strong inhibitory effect on IL-4- and anti-CD40 antibody-stimulated IgE production by human peripheral blood mononuclear cells (PBMCs). RNA analysis by both reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot showed that p6G5G1 inhibited germline Cε RNA synthesis, but had no effect on CD23 mRNA levels. These data suggest that p6G5G1 may inhibit immunoglobulin class switching to IgE through the inhibition of germline Cε RNA synthesis. Early addition of p6G5G1 after stimulation by IL-4 and anti-CD40 was critical for IgE inhibition. In contrast, later addition of p6G5G1 still showed inhibition of increased levels of surface CD23, which is normally upregulated by stimulation with IL-4 and anti-CD40.