Human CLA-1 is homologous to the mouse SR-BI gene, which was recently identified as a high density lipoprotein receptor involved in selective cholesterol uptake in rodent adrenal cells. We screened 42 normal and pathological adrenal samples by Northern blotting and found abundant expression of CLA-1 messenger ribonucleic acid (mRNA) in normal adult and fetal adrenals, adrenocortical adenomas, and hyperplasias. Adrenocortical carcinomas and the adrenals adjacent to Cushing's adenomas contained less CLA-1 mRNA than normal adrenals. CLA-1 mRNA was also highly expressed in a Leydig cell tumor, but much less in liver, kidney, and pheochromocytomas. The accumulation of CLA-1 mRNA in primary cultures of normal adrenocortical cells was up-regulated by ACTH in a dose- and time-dependent manner. Both dibutyryl cAMP and staurosporine increased the basal expression of CLA-1 mRNA. Although there was no additive effect of ACTH and dibutyryl cAMP, staurosporine slightly enhanced the stimulatory effect of ACTH on the expression of CLA-1 mRNA. The abundant expression of CLA-1 mRNA and its regulation by the physiological hormone ACTH in human adrenal cells suggest that CLA-1 has a role in adrenal steroidogenesis, probably as a lipoprotein receptor mediating the selective cholesterol uptake in these cells.