ATP is known to produce unusual modulations of catalytic steps in its own hydrolysis by sarcoplasmic reticulum ATPase both in the micromolar range and in the millimolar range of ATP concentration. The nature of these modulations can be probed with 18O-exchange techniques. Particularly valuable are recent approaches based on measurement of the [18O]Pi species formed from highly 18O-labeled ATP. Such analyses show that as ATP is decreased in the micromolar range there is a much greater tendency for reversal of hydrolysis of the phosphoryl enzyme prior to release of Pi to the medium. No modulation of steps involved in oxygen exchange is seen in the millimolar concentration range. Ways are presented in which the modulation at lower ATP could result from interaction of ATP at independent catalytic sites.