Previous studies indicate that the amplitude of 2f1-f2 distortion-product otoacoustic emissions (DPOAEs), evoked by two tones of frequencies f1 < f2, demonstrates a complex dependence on the levels (L1 and L2) of the primary tones. In the present study, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in normal human ears, allowing a systematic, level-dependent asymmetry of DPOAE amplitude in L1,L2 space to be characterized. The L1,L2 at which DPOAEs were largest was close to L1 = L2 at high stimulus levels, but moved monotonically toward L1 > L2 as stimulus levels decreased. A related observation was that DPOAE amplitude had a greater dependence on L1 and on L2. These asymmetries were quantified in normal human ears, and compared to the corresponding asymmetries apparent in data from animal models. Recent studies have demonstrated that the reduction of DPOAE amplitude by cochlear trauma is greater when L1 > L2 than when L1 = L2, suggesting that the reduction of DPOAEs by trauma demonstrates an asymmetry in L1,L2 space that is qualitatively similar to that of normative DPOAE amplitude. To investigate this issue, 2f1-f2 DPOAE amplitudes were measured over a wide range of L1 and L2 in rabbit ears pre- and postinjection of the ototoxic loop-diuretic ethacrynic acid. The results indicate that the asymmetry in L1,L2 space of the reduction of DPOAEs by trauma is both qualitatively and quantitatively similar to the asymmetry in L1,L2 space of normative DPOAE amplitude. Specifically, the L1 values that maximized normative DPOAE amplitudes for any specified L2 (or, equivalently, the L1 values that allowed L2 to be minimized for any specified normative DPOAE amplitude) also yielded the greatest reduction of DPOAEs by the diuretic. In humans, the L1 values that maximize normative DPOAE amplitudes for any specified L2 are well approximated by a simple equation, with parameters that vary with frequency and f2/f1. It is suggested that the L1,L2 values defined by this equation may be optimum for use in clinical applications.