Angioleiomyoma is frequently painful and the cause of the pain is unknown. The purpose of this study was to compare the mast cell population and innervation of painful and painless angioleiomyomas. Twenty-four cases of angioleiomyoma were examined; 16 painful and 8 painless cases. Pinacyanol erythrosinate and antibodies to protein gene product (PGP) 9.5 were used to demonstrate mast cells and nerves respectively. PGP 9.5-immunoreactive nerve fibres were found in most of the painful (13/16 cases) and painless lesions (5/8). Mast cells were not seen in half of the painful lesions but were seen in most of the painless lesions (7/8). The median mast cell density was 1.1 cells/mm2 for the painful lesions and 21.9 cells/mm2 for the painless lesions (P= 0.048, Mann-Whitney test). The lower mast cell density in the painful lesions may reflect increased mast cell degranulation. It is proposed that neural and vascular events, similar to those occurring in the triple response to mild cutaneous injury, may produce pain in angioleiomyoma and other painful skin tumours.