The influence of position of an alkyl in the aromatic bodies is well shown in ortho-, para- and meta-derivatives. Thus the author proved some years ago that with regard to disinfecting properties, ortho-cresol was more powerful than meta-; meta-cresol more powerful than para-; so again ortho-aceto-toluid is poisonous, causing acute nephritis; meta-aceto-toluid has but feeble toxic actions but is useful as an antipyretic; and para-aceto-toluid is inactive. In the trioxybenzenes, in which there are three hydroxyls, the toxic action is greater when the hydroxyls are consecutive, as in pyrogallol, than when they are symmetrical, as in phloroglucin. OH /\ / \ | |OH | | | |OH \ / \/ Pyrogallol. OH /\ / \ | | | | HO| |OH \ / \/ Phloroglucin. The introduction of methyl into the complicated molecule of an alkaloid often gives curious results: thus methyl strychnine and methyl brucine instead of producing tetanus have an action on voluntary muscle like curare. Benzoyl-ecgonine has no local anæsthetic action, but the introduction of methyl into the molecule endows it with a power of deadening the sensation of the skin locally; on the other hand, cocethyl produces no effect of this kind. Drs. Crum Brown and Fraser[35] have suggested that there is some relation between toxicity and the saturated or non-saturated condition of the molecule. [35] _Journ. Anat. and Phys._, vol. ii. 224. Hinsberg and Treupel have studied the physiological effect of substituting various alkyls for the hydrogen of the hydroxyl group in para-acetamido-phenol. Para-aceto-amido-phenol when given to dogs in doses of 0.5 grm. for every kilogr. of body weight causes slight narcotic symptoms, with slight paralysis; there is cyanosis and in the blood much methæmoglobin. In men doses of half a gramme (7·7 grains) act as an antipyretic, relieve neuralgia and have weak narcotic effects. The following is the result of substituting certain alkyls for H in the HO group. (1) =Methyl.=--The narcotic action is strengthened and the antipyretic action unaffected. The methæmoglobin in the blood is somewhat less. (2) =Ethyl.=--Action very similar, but much less methæmoglobin is produced. (3) =Propyl.=--Antipyretic action a little weaker. Methæmoglobin in the blood smaller than in para-acetamido-phenol, but more than when the methyl or ethyl compound is administered. (4) =Amyl.=--Antipyretic action decreased. The smallest amount of toxicity is in the ethyl substitution; while the maximum antipyretic and antineuralgic action belongs to the methyl substitution. Next substitution was tried in the Imid group. It was found that substituting ethyl for H in the imid group annihilated the narcotic and antipyretic properties. No methæmoglobin could be recognised in the blood.