Abstract: Since introduction of a methyl group in the 3-position of piperidine ring of 4-phenylpiperidine analgesics and replacement of phenylethyl group in the 1-position of piperidine ring of fentanyl by some substituents can enhance analgesic activity, we already synthesized some 3-methyl derivatives of fentanyl e. g., N-1-(2-phenylethyl)-3-methyl-4-piperidyl-N-phenylpropanamide(7209, simply named as 3-methyl fentanyl) and others (7207, 7222, 7210). In view of their higher analgesic activity than that of fentanyl, studies on derivatives of 3-methyl fentanyl were further performed. Pharmacological results showed that some compounds in this series have extremely potent analgesic activity with typical morphine-like action. The structure-activity relationships of these compounds are discussed, compound N-1-(2-hydroxy-2-phenylethyl-3-methyl-4-piperidyl-N-phenylpropanamide (7302) was found to be the most potent analgesic agent in this series. Its analgesic ED₅₀ value was 0.0022mg/kg and the analgesic activity was 28 times more potent than that of fentanyl and 6318 times than morphine.