Marihuana cigarettes containing 1.32, 1.97 and 2.54% .DELTA.9-tetrahydrocannabinol (THC) were smoked by 6 experienced [human] marihuana users at weekly intervals in a double-blind cross-over design under laboratory conditions. Puff duration, number of puffs taken, duration of inhalation holding, interval between puffs and duration of smoking were recorded for each cigarette smoked. The portion of each cigarette remaining after smoking was weighed and analyzed to determine THC content. Subjective ratings of the high achieved and the heart rate acceleration induced by smoking the marihuana were measured. The plasma concentrations of THC and of its principal metabolite, 11-nor-.DELTA.9-carboxylic acid (9-carboxy THC), were determined by radioimmunoassay of blood samples drawn at frequent intervals for 6 h. Irrespective of the potency of the marihuana, the pattern of smoking was much the same. The magnitude of the subjective high, heart rate acceleration, THC and 9-carboxy THC plasma concentrations were proportional to potency. This dose response was particularly clear between the 1.32 and the 2.54% cigarettes. Peak plasma concentrations of THC consistently occurred 7-8 min after initiation of smoking and declined thereafter despite continued smoking for another 6-10 min. Peak subjective high and peak heart rate acceleration occurred several minutes after the end of smoking and at a considerable interval after maximal THC plasma concentrations were reached.