Interleukin-1 (IL-1) is a member of a family of closely related molecules playing an important role in many inflammatory and immunologic reactions. Besides macrophages, epidermal cells such as keratinocytes release, either spontaneously or on stimulation, IL-1-like molecules also referred to as epidermal cell-derived thymocyte-activating factor (ETAF). In the present study, the potential role of the potent lipid mediator, platelet-activating factor (PAF), in the regulation of IL-1/ETAF release by keratinocytes was investigated. Keratinocytes from guinea-pig ears were incubated for 24 h in the presence or absence of lipopolysaccharide (LPS) and PAF, either alone or in combination. LPS markedly increased in a dose-dependent fashion the IL-1/ETAF release by keratinocytes, as assessed by the mouse thymocyte proliferation assay. In contrast, no effect of PAF on IL-1/ETAF release was observed. Simultaneous addition of 1 microgram/ml LPS and 1 pM PAF to keratinocyte culture increased IL-1/ETAF release compared to that observed with LPS alone. When 1 pM PAF was added 1 h before or 1 h after LPS, no effect on IL-1/ETAF release by keratinocytes was noted. In contrast, regardless of the time of addition of 10 fM PAF to keratinocytes stimulated with LPS (either simultaneously or 1 h after LPS), an identical and non-significant increase was observed. In conclusion, although PAF is not able to induce IL-1/ETAF release by keratinocytes, it potentiates that induced by a stimulus like endotoxin.