It is generally believed that the force for the otoacoustic emission (OAE) generation is provided by a mechanism of electromotility, observed in isolated cochlear outer hair cells (OHCs). OHC electromotility is resistant to several ototoxic reagents, it does not depend on ATP hydrolysis, but it can be blocked by specific sulfhydryl reagents: p-chloromercuriphenylsulfonic acid (pCMPS) and p-hydroxymercuriphenylsulfonic acid (pHMPS). We have used these reagents to test whether they also affect OAE. Application of pCMPS and pHMPS on the round window membrane of anesthetized guinea pigs produced a dose-dependent inhibition of the cubic (2F1-F2) distortion product OAE (DPOAE). The inhibition developed progressively from high to low frequencies, reflecting the diffusion of the drugs through the cochlear compartment. The effect of pCMPS and pHMPS was different from the effects of furosemide and lethal anoxia, which impair cochlear function but do not block OHC electromotility. pHMPS suppressed DPOAE completely at all sound intensities tested (45-80 dB SPL), whereas furosemide or lethal anoxia caused DPOAE to disappear at low-level stimulation (45-60 dB SPL) only. Our results suggest that the OHC electromotility might provide the force for DPOAE generation not only at low, but also at high stimulus intensities.