Small cell carcinoma of the lung is the tumor most commonly associated with ectopic ACTH production and hypercortisolism. The relationship between this paraneoplastic endocrine syndrome and the clinical course of the tumor is examined in this review of patients with the ectopic ACTH syndrome and small cell carcinoma seen at The Johns Hopkins Oncology Center between 1973 and 1979. Five of 157 (3.2%) patients with small cell carcinoma were clinically diagnosed as having the ectopic ACTH syndrome. The onset of this endocrine syndrome appeared to coincide with a more aggressive phase of the course of small cell carcinoma. Further analysis of these cases suggests that the development of the ectopic ACTH syndrome may reflect changes in cell populations within the tumor and/or alterations in tumor behavior with time and perhaps with the effects of drug therapy.