Structure-activity relationships between histamine and nicrotine are described. If alkyl groups are substituted on the primary amino group of the side chain in histamine the histamine-like action decreases stepwise. While N,N-diethylhistamine (I) clearly shows histamine-like activity, 4-(2-pyrrolidinoethyl)-imidazole (II), an analogue having a pyrrolidine ring in place of the diethylamino group, possesses, on the other hand, distinct nicotine-like properties. The ganglionic stimulation was investigated on the isolated ileum of the guinea-pig, as well as on the blood pressure of the narcotized rat. The nicotine-like effects remained as the imidazole ring was replaced with a pyridine or benzene ring. These results make it plausible to assume that the effect of nicotine-like acting substances is due to an angular conformation, corresponding to nicotine.