Four patients (two males and two females, ages 12-21 years) had clinical features of the Cushing syndrome. Results of biochemical tests (in three patients tested) suggested the presence of an autonomously functioning adrenocortical neoplasm. However, radiologic examination of the adrenals did not show an adrenal tumor. The four patients underwent curative bilateral total adrenalectomy and did not manifest the Nelson syndrome postoperatively (follow-up, 2-22 years). The adrenal pathologic findings in these patients were similar. Gross findings included: 1) decreased, normal, or slightly increased total gland weight; 2) studding of the external and cut surfaces by small (less than 4 mm) black, brown, dark-green , red, or (rarely) yellow nodules; and 3) cortical atrophy and disorganization of the normal zonation between the nodules. Microscopically, the nodules were composed predominantly of enlarged, globular, cortical cells with granular eosinophilic cytoplasm that often contained lipofuscin. Twenty-four similar cases have been reported. Findings in these plus our four cases identify a special type of adrenocortical pathology associated with Cushing syndrome, for which we suggest the name "primary pigmented nodular adrenocortical disease."