Microgravity-induced changes in the bioavailability of drugs may influence the efficacy or toxicity of drugs. The bioavailability of orally administered drugs may be altered by changes in dissolution rate, intestinal microflora, intraluminal enzymes, epithelial enzymes, rate of passage across the gastrointestinal epithelium, gastric emptying rate, intestinal transit time, hepatic first pass metabolism, and gastrointestinal and hepatic blood flow. Limited data from antiorthostatic bed rest and inflight studies provide preliminary evidence that the bioavailability of orally administered drugs in space may be decreased or subject to more interindividual variation than expected from ground-based studies.