Several groups have previously reported that rodent or human leukemic mast cells produce inflammatory cytokines such as TNF‐α and IL‐8 as well as the pro‐allergic cytokines IL‐4, IL‐5 and IL‐13. Comparatively little is known, however, regarding the ability of normal human skin mast cells to secrete these factors following either IgE‐dependent or IgE‐independent modes of activation. We therefore investigated whether normal human skin mast cells produce these cytokines following stimulation by a variety of secretagogues. Enriched isolated skin mast cells released both TNF‐α and IL‐8 following activation with either anti‐IgE, SCF, substance P, compound 48/80 or A23187. This release was dose‐ and time‐dependent, with maximal levels being reached within 4 h of stimulation involving, in part, the secretion of preformed stores of both cytokines. In accordance with this, using lysates of highly purified (>90%) skin mast cells, we could demonstrate that both TNF‐α and IL‐8 mRNA and protein were present in both unstimulated as well as stimulated mast cells. In stark contrast to these results, no significant levels of either IL‐4, IL‐5 or IL‐13 were detected, regardless of the secretagogue used or the period of stimulation. These results show that human skin mast cells are capable of rapidly secreting pro‐inflammatory cytokines like TNF‐α and IL‐8 following IgE‐dependent activation and stimulation by the neuropeptide substance P, SCF and the basic polypeptide analogue compound 48/80. In contrast to other types of human mast cells however, human skin mast cells were incapable of secreting IL‐4, IL‐5 or IL‐13 in these settings.