Transgenic mice overexpressing platelet-activating factor receptor (PAFR) have abnormal pigmentation of the ear and the tail, which can progress to melanocytic tumors as the mice age. Histologically, epidermal hyperproliferation and increases in dermal melanocytes are evident. Examination of these transgenic mice at various ages revealed hyperproliferation of the epidermis even 2 weeks after birth which developed as the mice aged. Dermal melanocytes also increased in number with growth. Expression of the PAFR transgene was found in keratinocytes and not in melanocytes, thereby suggesting that PAF does not play a direct role in proliferation of melanocytes. Topical application of a cream containing WEB2086, a specific PAFR antagonist, to the ear and the dorsal skin significantly suppressed the number of BrdU-positive cells in PAFR transgenic mice. These results suggest that PAF plays a modulatory role in the growth of epidermal keratinocytes. PAFR transgenic mice would be a useful model for investigations of skin diseases related to altered proliferation of epidermal keratinocytes including psoriasis.