Rhinophyma represents a severe variant of rosacea, a common mid-facial erythematous dermatosis. Increased blood flow and pooling in skin are thought to be involved in its pathogenesis. Since neuropeptides and their receptors are responsible for local blood flow regulation, immunolocalization for the vasoactive intestinal peptide (VIP)-receptor(R) was performed in slice biopsies taken from five patients with glandular rhinophyma. Additional immunostainings included intermediate filaments (keratin, vimentin) and neuroglandular antigen (NGA). In contrast to controls, rhinophyma disclosed not only a more dense distribution of VIP-R positive cells within the endothelium but immunoreactive perivascular large cells. The immature sebocytes stained positive with monoclonal antibody Cam5.2 against glandular antigens and polyclonal anti-S100A. Elastotic connective tissue in the dermis showed a strong immunoreactivity for vimentin and NGA. From these results we suggest that, (a) ligands of the VIP-R may contribute to vascular and dermal alterations in rosacea and (b) immature sebocytes show an unusual antigen expression of S100A and glandular keratin.