1. The Spectrum of effects produced with single doses of N,N- dimethyltryptamine (DMT) in 6 nontolerant human subjects resembled those produced with lysergie acid diethylamide (LSD). Either drug produced an elevation in systolic blood pressure, a decrease in the threshold for the kneejcrk, pupillary dilatation, and a mental response characterized by anxiety, perceptual distortions and hallucinations. The onset and duration of action was shorter with DMT (0.5 mg/kg) as compared to LSD (1.5meg/kg), but the maximum intensity of effects with respect to each parameter was equivalent for both drugs. 2. Following the chronic administration of LSD only a mild degree of cross tolerance to the mental response could be demonstrated with DMT (0.5 mg/lkg) in subjects highly tolerant to tile pupillary, kneejerk, and mental effects of LSD (3.0 mcg/kg). 3. It is inferred that the site or mechanism which is altered during LSD tolerance is not one which is primarily concerned with the action of DMT.