The rate constants of hydrolysis of a series of 4-substituted phenyl propionates, catalysed by bile-salt-stimulated human milk lipase in the absence and presence of cholate or taurocholate stimulation, have been measured at pH 7.3, 310.5 K. There is little evidence for an alkyl site electronic interaction in the rate-determining step of the esterolytic reaction. However, a negatively charged substrate or an amido-substituent caused an inhibition of unstimulated esterase activity. In the presence of the bile-salt cofactors, esterolytic activity against charged substrates may be stimulated or inhibited, depending on the proximity of the charge to the steroidal side chain and the subsequent substrate-interaction within the surrounding environment of the active site. It has been confirmed that bile-salt- stimulated lipase is not an amidase , but that an amide, of the correct geometry, may occupy the active site and restrict esterase activity.