One key unresolved issue in immunoglobulin class switch recombination (CSR) is how the accessibility of the switch region for CSR is controlled. To better understand the nature of accessibility control for human Ig CSR, we developed a novel inducible switch recombination assay based on expression of green fluorescence protein (GFP) from switch constructs undergoing substrate switch recombination (SSR). Efficient SSR depends on the cytokine‐inducible Iϵ promoter and co‐stimulation with IL‐4+anti‐CD40. Characterization of SSR reveals that both S‐S deletional recombination and S‐Sinversion occur. We show that the IL‐4‐inducible Iϵ promoter (pIϵ) selectively determines the efficiency of the accessibility for SSR. However, the pIϵ‐induced transcription, by itself,is not sufficient to direct efficient SSR. For efficient SSR, both pIϵ‐driven transcriptional activity and an additional promoter/enhancer‐derived activity are required. The efficiency of SSR is not tightly correlated with the strength of the combined transcriptional activity. Our results suggest that the mechanism(s) underlying the transcriptional activity, e.g. DNA modification is important for controlling the accessibility for efficient switch recombination.