The aim of this study was to reveal the origin of interleukin cascade reaction disturbances in pemphigus vulgaris (PV) and bullous pemphigoid (BP). We investigated the influence of culture supernatant of epidermal keratinocytes from the skin of PV and BP patients on functional activity of donor peripheral blood mononuclears. It was found that epidermal keratinocyte culture supernatant in the acute phase of PV and BP decreased the ability of mononuclears to proliferate in response to PHA and Con A, secrete interleukin-1 and interleukin-2, and absorb an exogenous interleukin-2. Such inhibitory effect was far less pronounced in epidermal keratinocytes obtained from PV and BP patients at the remission stage. Epidermocytes from healthy subjects stimulated the immunocompetent cell activity. The results obtained indicate that epidermal keratinocytes in the acute phase of pemphigus and pemphigoid produce a putative soluble factor(s), which may be the origin of the immunodeficiency in PV and BP patients.