Force generated by outer hair cells is thought to be an essential source of mechanical input to the normal cochlea. Many disease processes in the inner ear act via outer hair cells. It is therefore plausible that such disease processes modulate outer hair cell force generation. The force generated by an isolated, electrically stimulated outer hair cell against a load may be represented by an intrinsic motor and a passive axial stiffness in series. Thus modulation of outer hair cell force generation may occur either by action on the motor or indirectly by an action on cell stiffness. In this study, the effects of agents that affect hearing on outer hair cell stiffness and force generation have been examined. Overstimulation and hypoosmotic challenge caused cells to decrease in length and increase in stiffness. The force generated by a constant voltage stimulus increased consequent to the stiffness increase. Hyperosmotic challenge elicited a stiffness decrease and a force decrease. In contrast, salicylate caused a decrease in force without stiffness change. The results suggest that outer hair cell force generation in vivo may be modulated in at least two ways.