The biodistribution of 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) was assessed in hypercholesterolaemic patients and in a rabbit model of HC to examine the alterations in the relative distribution of NP-59 and its metabolites and to explain the changes in the patterns of adrenal cortical imaging in patients with expanded cholesterol pools. Rabbits were rendered hypercholesterolaemic with a diet supplemented with 2% cholesterol for 2 weeks prior to the intravenous administration of 240 to 570 microCi of NP-59. Adrenal, bile and serum samples were obtained from four hypercholesterolaemic rabbits at 48 h following NP-59 administration, and the distribution of 131I radioactivity was compared to that of seven rabbits maintained on a standard laboratory diet. Serum cholesterol levels were 1940 +/- 248 mg dl-1 in the hypercholesterolaemic rabbits as compared to 268 +/- 62 mg dl-1 in the controls. Adrenal cortical uptake of NP-59 was decreased in HC rabbits but no significant differences were observed in the relative proportions of NP-59 or its metabolites in the bile and adrenal tissues of hypercholesterolaemic versus control animals. Hypercholesterolaemic animals did exhibit an increase in NP-59 esters in serum as compared to controls. In three of five patients with hypercholesterolaemia, adrenal uptake of NP-59 was enhanced after successful lowering of serum cholesterol levels, while the remaining two patients who responded inadequately to cholesterol-lowering therapy showed a slight drop in NP-59 uptake.