The salinity tolerance of the 'California' Mozambique tilapia (Oreochromis mossambicus x O. urolepis hornorum), a current inhabitant of the hypersaline Salton Sea in California, USA, was investigated to identify osmoregulatory stress indicators for possible use in developing a model of salinity tolerance. Seawater-acclimated (35 g l(-1)) tilapia hybrids were exposed to salinities from 35-95 g l(-1), using gradual and direct transfer protocols, and physiological (plasma osmolality, [Na+], [Cl-], oxygen consumption, drinking rate, hematocrit, mean cell hemoglobin concentration, and muscle water content), biochemical (Na+, K(+)-ATPase) and morphological (number of mature, accessory, immature and apoptotic chloride cells) indicators of osmoregulatory stress were measured. Tilapia tolerated salinities ranging from 35 g l(-1) to 65 g l(-1) with little or no change in osmoregulatory status; however, in fish exposed to 75-95 g l(-1) salinity, plasma osmolality, [Na+], [Cl-], Na+, K(+)-ATPase, and the number of apoptotic chloride cells, all showed increases. The increase in apoptotic chloride cells at salinities greater than 55 g l(-1), prior to changes in physiological and biochemical parameters, indicates that it may be the most sensitive indicator of osmoregulatory stress. Oxygen consumption decreased with salinity, indicating a reduction in activity level at high salinity. Finally, 'California' Mozambique tilapia have a salinity tolerance similar to that of pure Mozambique tilapia; however, cellular necrosis at 95 g l(-1) indicates they may be unable to withstand extreme salinities for extended periods of time.