An increasing body of evidence suggests that insulin-like growth factors (IGFs) are important in the development of some tumors. In the present study, we investigated the gene expression of IGF-I, IGF-II, and their receptors in different adrenal tumors and hyperplasias. Four adrenocortical carcinomas, 15 adenomas, 4 pheochromocytomas, 5 nodular hyperplasias, and hyperplastic adrenals from 2 patients with pituitary Cushing's disease were analyzed and compared to normal adrenals. Northern blots, dot blots, and reverse transcription polymerase chain reaction analyses were used for mRNA detection, and immunohistochemistry was used for IGF-II peptide localization. The IGF-I mRNA content was low in normal, hyperplastic, and neoplastic adrenals. IGF-II mRNA levels were more than 10-fold higher in hormonally active adrenocortical carcinomas than in normal adult adrenals, and increased IGF-II-like immunoreactivity was detectable in these carcinomas. A moderate elevation of the IGF-II mRNA content was also noted in one nonfunctioning carcinoma. The IGF-II mRNA content was high in pheochromocytomas, as reported previously. Furthermore, Cushing's and Conn's adenomas expressed IGF-II mRNA levels similar to those in the normal adrenal. In nodular adrenocortical hyperplasia, we found variable IGF-II mRNA content (40-400% of normal adrenal expression). All of the normal adrenal and tumor tissues studied contained both the type I and type II IGF receptor mRNAs. The findings in the present study show that both IGF-I and IGF-II and their receptor mRNAs are expressed in various adrenocortical tumors. Moreover, the high IGF-II expression in functional adrenocortical carcinomas suggests that the IGFs may be involved in the auto/paracrine regulation of certain adrenocortical tumors.