AbstractOn account of the high activity reported for 2,3,6‐trichlorobenzoic acid (BentleyJ. A. Bentley, Nature165, 449 (1950).)), at first sight lacking the spatial relation between—COOH group and ringsystem occurring in the active compounds known until now, the series of substituted benzoic acids was studied more closely. From the six isomeric trichlorobenzoic acids, now investigated in the pea‐test, only the 2,3,6‐trichloro acid proves to be highly active. From their U.V.‐absorption spectra it is deduced that with the di‐ortho (2,6) substituted acids steric inhibition of resonance occurs. In this way the tendency of the molecule to occur in a flat form on account of conjugation is counteracted. Consequently in the undissociated acid the dipole vector of the —COOH group will be at an angle with the plane of the ringsystem. For this reason the active substitued benzoic acids are considered in essence to be equivalent to the types of active compounds studied before, realizing a three‐dimensional amphipatic structure in a special way, namely by steric inhibition, especially of factors favouring coplanarity. 2,6‐Dichlorobenzoic acid, showing the same inhibition, is found to be physiologically active too and arguments are given that very probably the weak activity of α‐naphthoic acid has to be explained along the same lines. When in the latter acid the steric inhibition of resonance is intensified (as appears from the U.V.‐spectra) by chlorine‐substitution in the β‐position, for the resulting β‐chloro‐α‐naphthoic acid an increased activity is found, this being practically the same as