Upon melittin stimulation, cultured SCC-13 keratinocytes release prostaglandins E2, F2 alpha, 6-keto-F1 alpha, thromboxane B2, leukotriene B4, and 6-sulfido-peptide-containing leukotrienes (SRS) into serum free medium. Release of prostaglandins E2, F2 alpha, and SRS, normalized to cell protein, is 3- to 10-fold higher from rapidly growing than confluent cultures. Cells growing with hydrocortisone in the medium produce approximately twice the level of the cyclooxygenase-mediated metabolites PGE2 and PGF2 alpha as those without hydrocortisone, but similar levels of the lipoxygenase-mediated metabolite SRS. The results demonstrate the potential utility of squamous carcinoma lines for investigating biochemical pathways of arachidonic acid metabolism in keratinocytes.