PGP 9.5 is a soluble protein isolated from brain and is a general marker for neuronal and neuroendocrine tissue. Its function is not known. Until now neurone specific enolase (NSE) has been the only general marker for the paracrine system and tumours derived from it. Seventy-four neuroendocrine tumours, 17 melanocytic naevi, 51 melanomas and four granular tumours were stained immunohistochemically for PGP 9.5 and NSE. A variety of pulmonary and non-neuroendocrine tumours were also stained. Two so-called goblet cell carcinoids of the appendix were included in the series. Using NSE 59/74 neuroendocrine tumours were positive and 58/74 stained for PGP 9.5. In combination 63/74 of these tumours were positive for either NSE or PGP 9.5 or both. Staining for PGP 9.5 was better for demonstration of nerves in routinely processed material than was staining for NSE. Twenty-one out of 43 primary melanomas stained for PGP 9.5 and 36 showed staining for NSE. Only two of eight metastatic melanomas melanocytic stained for PGP 9.5 while seven of these eight stained for NSE. Six of 17 melanocytic naevi stained for PGP 9.5 and five stained for NSE. All four granular cell tumours stained for PGP 9.5 and NSE. Both "goblet cell carcinoids' of the appendix were negative for NSE and PGP 9.5. Fifteen out of 32 pulmonary cancers showed staining for either marker and no non endocrine tumour showed any specific staining. Staining for PGP 9.5 is a valuable additional probe in the exploration of the paracrine system and the diagnosis of tumours arising from it.