Hydroxypropyl cyclodextrins are nontoxic carbohydrate derivatives of moderate molecular weight (1030-1750 Da) which form water-soluble complexes with many lipophiles. The fate of hydroxypropyl beta-cyclodextrin alone and in complex with testosterone or cholesterol injected intravenously or intracerebrally into rats was followed. More than 90% of intravenously administered hydroxypropyl beta-cyclodextrin was cleared into urine in 4 h, as previously described (Monbaliu, J.; Van Beijsterveld, L.; Meuldermans, W.; Szathmary, S.; Haykants, J. Abstracts, 5th International Symposium on Cyclodextrins, Paris, 1990; Abstract 65). After the injection of steroids in complex with hydroxypropyl beta-cyclodextrin into the tail vein of rats, the steroid component was released from the complex, before it reached the kidneys; the release occurred mainly into the proteins and lipoproteins of serum. Hydroxypropyl beta-cyclodextrins injected alone into the brain were cleared within less than 24 h, presumably via the flow of interstitial and cerebrospinal fluids, and eventually were excreted in urine. Testosterone, incorporated in a hydroxypropyl beta-cyclodextrin complex, after intracerebral injection was cleared from the brain even more rapidly than hydroxypropyl beta-cyclodextrin, presumably by crossing the blood-brain barrier and later removal to the liver by the specific carrier proteins in serum. Complexed cholesterol, in a similar experiment, was largely retained in the brain and its distribution there was uneven and remained that way for at least 3 days. It is clear that lipophilic agents, after their incorporation into hydroxypropyl beta-cyclodextrin complexes and subsequent in vivo administration, are rapidly released and exchanged into the plasma. In absence of plasma they enter tissues surrounding the injection site and thus are also promptly transferred into the organism's lipid systems. The manner in which different lipophilic agents are transported in vivo appears not to be greatly affected by their previous complexation; rather hydroxypropyl cyclodextrins just enable their entry in a larger amount and in an exchangeable, nonaggregated form.