Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production.