The mechanism of the inactivation of prostatic acid phosphatase (PAP) by 4-halomethylaryl phosphates, such as 4-(fluoromethyl)phenyl phosphate (FMPP), was probed by varying the benzylic leaving group and adding a nitro group to the 2 position. These studies demonstrate that both the rate and efficiency of inactivation are dependent on the nature of the leaving group in the benzylic position, with the brominated inhibitor being the most effective (t(1/2) = 11 s), the chloride being less effective (t(1/2) = 200 s), and the fluoride showing little or no inhibition. The addition of a nitro group to the 2 position of the benzene ring of the inhibitor results in high selectivity for the inactivation of prostatic acid phosphatase over PTPases like YOP51*. This pattern of selectivity contrasts with that of FMPP which quickly inactivates both prostatic acid phosphatase and YOP51*. The potential uses of these types of mechanism-based inactivators are discussed.