Complex formation of diazepam and of naproxen with β-cyclodextrin results in increased aqueous solubility of the drug. The complex stability constants found were 179 and 2146 M-1, respectively. To study the effect of complex formation of drugs with β-cyclodextrin in vivo, micro-enemas containing diazepam or naproxen with and without β-cyclodextrin were administered to human volunteers. Plasma levels of the drug were determined for the investigation of the absorption of the two drugs. The results demonstrated that absorption neither of cyclodextrin nor of the drug-cyclodextrin complex took place, and that a decrease in the rate of absorption of the drug did not occur when administered as the drug-cyclodextrin complex. The absence of absorption deceleration was explained by the fact that complexed drug is displaced from the complex by lipids in the mucus adjacent to the absorption membrane. The ability of mucus and bile samples to displace complexed drug was shown in vitro in displacement studies with phenolphthalein. Especially bile was shown to possess a high capacity for displacement. The micro-enemas in which all drug was dissolved through complexation showed much faster absorption as compared with those in which the drug was suspended.