The effect of sleep on the bioavailability of tetracycline was studied using 250-mg tetracycline hydrochloride capsules from two commercial sources. One capsule of each brand was given to each of 12 healthy volunteers on two separate occasions. On one occasion, the subject ingested the drug upon arising in the morning and remained ambulatory (ambulatory trial). On the other, the subject awakened during the night, ingested the capsule, and resumed sleep (sleep trial). Bioavailability was assessed from the cumulative amount of drug excreted in the urine during the 96 hr following drug intake. While there was no significant difference in the bioavailability of one brand between the ambulatory and sleep trials, the bioavailability of the other decreased an average 27% ( p < 0.01) in the sleep trial. Also, the difference between the bioavailability of the two preparations was not discernible in ambulatory subjects, but it was statistically significant ( p < 0.05) in the sleep trial. The impaired bioavailability appears to result from decreased dissolution of one brand in the high gastric pH occurring at night. These findings raise questions as to the predictability of bioavailability studies in ambulatory subjects relative to the actual use of drug products, which are frequently administered during conditions of bed rest or sleep. Keyphrases Tetracycline-bioavailability, different commercial capsules, effect of sleep, humans Bioavailability-tetracycline, different commercial capsules, effect of sleep, humans Sleep-effect on bioavailability of tetracycline, different commercial capsules, humans Antibacterials-tetracycline, bioavailability, different commercial capsules, effect of sleep, humans ' Lot 202-101, Lederle Labs, Pearl River, N.Y. Lot 29/G, Gvma Lab.. Forest Hills. N.Y. :' Chemical assay indicated that the'amounts of drug present in Brands A and B were 262 and 258 mg, respectively.