A series of 12 carcinoid tumours of the appendix were examined with regard to S-100 protein immunoreactivity. All tumours were both argentaffin and argyrophil, and displayed immunoreactivity after application of a monoclonal antibody against serotonin. The S-100 protein immunoreactivity appeared in 11 of the 12 tumours, preferably in cells presumably of Schwann cell origin with long slender processes localized at the periphery of the carcinoid tumour buds. Immunoreactive cells with cytoplasmic processes were also seen extending between individual tumour cell in the tumour aggregates. In a few tumours S-100 immunoreactivity occurred in the cytoplasm of tumour cells with or without cytoplasmic extensions. The presence of S-100 protein immunoreactive cells, apparently as an integral component, and its shape and distribution indicate that the peripheral nervous system (PNS) is histogenetically involved in the development of carcinoid tumours of the appendix.