It is known that an individual's drug use history affects the quality of subjective effects experienced following administration of several clinically used psychoactive drugs such as barbiturates, diazepam, and morphine. However, it is not known whether drug use history also affects responses to therapeutic cannabinoids such as delta9-THC. The current experiment compared the subjective and behavioral effects of oral delta9-THC in two groups of volunteers: frequent users (FREQ; n = 11), who reported using marijuana at least 100 times, and infrequent users (INF; n = 10) who reported using marijuana 10 or fewer times. Subjects participated in three sessions during which they received delta9-THC (7.5 and 15 mg) and placebo. They completed subjective effects questionnaires for 5 h following administration. In the FREQ group, the lower dose (7.5 mg) increased ratings of "feel drug," relative to placebo, whereas it had no effect in the INF group. In contrast, at the higher dose (15 mg), ratings of "feel drug" were lower in the FREQ group than in the INF group, suggestive of tolerance. In addition, the INF group reported greater sedative effects than the FREQ group following the higher dose of delta9-THC, again suggesting tolerance to delta9-THC's sedative effects. These findings demonstrate that marijuana use history may affect the subjective effects of oral delta9-THC, but that the influence of drug use history depends on the dose of drug administered. These findings may have implications for the clinical use of delta9-THC and other cannabinoids.