Nine patients with uncomplicated acromegaly showed the cerebrospinal fluid (CSF) human growth hormone (HGH) to be 0.49±0.11 ng/ml (mean±sem) as compared to 8 control subjects whose values were extremely low (<0.09±0.01 ng/ml), with the majority below the sensitivity limit of the assay. Three other patients with suprasellar extension of the pituitary mass showed a 140- to 800-fold greater value of HGH in CSF as compared with the uncomplicated group. The invariably high levels of HGH in CSF in acromegaly, particularly associated with suprasellar extension of the pituitary mass, indicate that a large peptide hormone can cross the blood-CSF barrier. This measurement appears to have potential usefulness in the clinical evaluation of acromegalic patients.