Epidermal infiltration by polymorphonuclear cells is a prominent feature in psoriatic lesions. Expression of neutrophil-specific chemoattractants by lesional keratinocytes could play an important role in the regulation of this infiltration process. We therefore examined the mRNA expression of GRO-α, a well-characterized peptide with neutrophil-specific activation profile in psoriatic lesions by in situ hybridization. Clusters of clearly detectable and in some cases highly abundant GRO-α hybridization signals could be demonstrated in the differentiated layers of psoriatic epidermis. The signals were clearly associated with keratinocytes, with no nearby neutrophils detectable by microscopic examination. When additional tissue sections of GRO-α-expressing lesions were examined with an interleukin-8/neutrophil-activating peptide-8 (IL-8)-specific anti-sense probe, IL-8 expression was detectable and confined to areas also expressing GRO-α. Expression of both GRO-α and IL-8 is focally upregulated by an as yet unknown mechanism in lesional psoriatic keratinocytes, ultimately leading to neutrophil tissue infiltration. We suggest that the focal expression of GRO-α and IL-8 in the epidermal layers above the dermal papillae may be involved in the “squirting papilla” reaction described as a characteristic feature of psoriatic plaque type lesions.