Phaeochromocytoma is an occasional cause of the ectopic ACTH syndrome. The mechanisms of proopiomelanocortin (POMC) gene expression were analysed in 11 human tumours not associated with Cushing's syndrome, by detecting and characterizing the POMC mRNA. A DNA probe corresponding to most of the protein-coding region of the third exon was used in Northern blot studies of total and poly(A)+ RNA. All tumours contained a short (800 bases) mRNA species different from the 1200 base mRNA species of the human pituitary. This short mRNA was also present in the normal adrenal, where S1 mapping showed that it resulted from transcription initiation within the third exon. However, in two tumours, equivalent amounts of the 1200 base mRNA were also present, and in one of them a third POMC mRNA of approximately 1450 bases was detected. These data show that POMC gene expression occurs in all phaeochromocytomas. It is suggested that excess production of the 1200 bases (or the larger, 1450 base) mRNA in some tumours may be responsible for the rare occurrence of the ectopic ACTH syndrome.