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Introduction: The absorption process is an essential stage that determines the bioavailability of xenobiotics during extravascular administration. The intensity of absorption depends on numerous factors not necessarily related to the substance and its formulation, and also on biotransformation and active transport processes. Methanol and its water solutions facilitate the animal dosage of several drugs, inhibitors and other xenobiotics in a soluble form while these compounds are not soluble in water. However, during administration of small amounts of drugs, the effect of vehiculum on drug fate in the body becomes also evident. Material and Methods: The study was performed on male Wistar rats cmd(WI)WU. Phenacetin was given per os in a single dose of 100 mg/kg b.w. Various procedures of phenacetin administration were tested, including solubilization in methanol and/or suspension in 1% water solution of carboxymethylcellulose. A three-hour pretreatment with 75% methanol solution before phenacetin administration was also applied. Serum concentrations of phenacetin and acetaminophen, its metabolite, were determined by HPLC method with solid phase extraction. Results and Conclusions: The presented results indicate that methanol decreases blood acetaminophen concentrations and phenacetin bioavailability. These changes appeared immediately after methanol exposure, but during the last four weeks of the experiment, when methanol was not in use, and only phenacetin in 1% carboxymethylcellulose was administered to rats, the decrease in phenacetin biotransformation and bioavailability was maintained. [ABSTRACT FROM AUTHOR]