Skin from the upper lip, bearing the sinus hair follicles rich in Merkel cells was investigated in guinea pig, rat, cat and rabbit by radioimmunoassay and radioreceptor assay. In all species Met-enkephalin-like immunoreactive material was extracted. In guinea pig this material had the same molecular size as Met-enkephalin. In a radioreceptor assay made with rat brain membranes extracts of guinea pig skin caused displacement of [3H]Met-enkephalin. The endogenous opioid of the size of Met-enkephalin contained in these skin extracts possibly derives from the Merkel cells.