Structure-activity relationship studies on two mescaline analogues have been conducted, using rats trained on a CAR buzzer-shock schedule. 3∶4-dimethoxyphenylethylamine has been shown to depress the CAR with an apparent bimodal distribution of peak activities, in contrast to the biphasic inhibitory and excitatory effect of mescaline. The effect of this dimethoxy compound is similar to that previously reported for a protein fraction from schizophrenic plasma; this is of particular interest as six groups have recently reported the isolation of this compound from schizophrenic urin