A comprehensive knowledge of the structure-activity relationship in the psychotomimetic compoounds should throw some light on their mode of action. The behavioural effects of some analogs of mescaline and N,N-Dimethyltryptamine have been studied in the rat. Both these compounds produce a characteristic biphasic effect on reaction-time as measured on shuttle-box avoidance. The nature of these drugs profiles in the rat parallels the quantitative differences in the course of action of the two drugs in man. Several mescaline-like compounds with ring-hydroxy groups were tested and none of these produced biphasic responses. The tryptamine analogue 5-methoxy-N-methyltryptamine was found to be almost inactive whereas 5-methoxy-N,N-dimethyltryptamone produced a biphasic response greater tha tthat of DMT.