This review of the disposition of methamphetamine in oral fluid, plasma, and urine is based on a comprehensive controlled dosing study involving five healthy, drug-free research volunteers who resided on a closed clinical ward for 12 weeks. Subjects were administered four low (10 mg) and high (20 mg) daily oral doses of methamphetamine in two separate sessions. Near-simultaneous collections of oral fluid and plasma were performed on the first day of each low- and high-dose session. Thereafter, oral fluid was provided on each day of dosing by different oral fluid collection methods. All urine specimens were collected on an ad libitum basis throughout the study. Specimens were analyzed by gas-chromatography mass spectrometry for methamphetamine and the metabolite, amphetamine, with a limit of quantification of 2.5 ng/mL for each analyte. Methamphetamine and metabolite concentrations in oral fluid appeared to follow a similar time course in oral fluid as in plasma and were dose-proportional, but oral fluid concentrations exceeded plasma concentrations. Urine drug concentrations were substantially higher than those in oral fluid. Some drug accumulation was noted with daily dosing, but generally did not markedly influence detection times or detection rates of oral fluid tests. Detection times and detection rates for oral fluid and urine were determined at cessation of 4 days of dosing. Generally, detection times and rates for urine were longer than those observed for oral fluid at conventional cutoff concentrations. When contemplating selection of oral fluid as a test matrix, the advantages of oral fluid collection should be weighed against its shorter time of detection compared to that of urine.