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The purpose of this study was to characterize the pharmacokinetics of a subcutaneously implanted tissue-chamber model. Thermoplastic tissue chambers were implanted in the paralumbar fossae of six steers. Starting 30 days after implantation, the distribution of intravenously administered antipyrine and phenylbutazone into the tissue chambers was studied. These pharmacokinetic experiments were repeated 10 days later to determine the effect of time after implantation on tissue-chamber distribution. Fifty days after implantation, tissue chambers were drained of transudate, refilled with sterile saline and the rate of influx of endogenous urea, creatinine and albumin was measured. Delayed diffusion of antipyrine and phenylbutazone into tissue chambers was well described using a compartmental model in which tissue-chamber fluid represented the third of three compartments arranged in series. The distribution of antipyrine into tissue chambers was greater than that of phenylbutazone; an observation which is well correlated with the high degree of protein binding of phenylbutazone. There was no effect of time on the penetration of the two agents. Rapid diffusion of urea and creatinine and extremely slow influx of albumin into chambers showed that these chambers formed true interstitial compartments.