Large molecular weight (oligomeric) forms of human growth hormone (hGH) are present in both pituitary extracts and plasma, but the origin of the plasma forms is not known. We used a monoclonal anti-hGH antibody (No. NA-71), previously employed to characterize hGH oligomers in pituitary extracts, to examine circulating hGH oligomers. This monoclonal antibody discriminated between monomeric and polymeric hGH forms in the pituitary. Plasma from normal subjects and acromegalic patients was fractionated by Sephadex G-100 chromatography and fractions were assayed by a monoclonal radioimmunoassay (RIA) using antibody NA-71 and by a polyclonal RIA. The oligomeric plasma hGH fraction showed decreased immunoreactivity in the monoclonal RIA, similar to that observed with pituitary oligomers. The immunopotency ratios of the various plasma hGH size isomers, as determined in the two RIAs, were virtually identical to those of pituitary hGH size isomers. We conclude that circulating hGH oligomers are immunochemically indistinguishable from pituitary hGH oligomers, and thus are most likely derived from pituitary stores.