The whole-cell patch clamp modes were developed to investigate the ionic channels of cellular membrane and to elucidate the signal transduction pathways from receptor to effector. The nystatin perforatedpatch mode in particular, can reveal detailed characteristics of intracellular signaling pathways which were involved in GTP binding proteins (G proteins) and second messengers. This review describes the recent studies of intracellular signaling pathways in dissociated outer hair cells (OHCs) of guinea-pig cochlea by using both the conventional whole-cell mode and the nystatin perforated-patch mode. Substance P (SP) response, decreasing the non-selective cation channel conductance, was involved in pertussis toxin (PTX)-insensitive G protein, but not in any second messengers. Acetylcholine (ACh) response, opening the Ca2+-dependent K+ channels, was involved in both PTX- and cholera toxin (CTX)-sensitive G proteins through IP3 pathway and cAMP pathway respectively. The possible intracellular signaling pathways in OHCs of guinea-pig cochlea were discussed in accordance with present results.