Cultured chick embryo cardiac myocytes submitted to a 180mOsm/kg hyposmotic solution swell present a regulatory volume decrease (RVD). This RVD is mediated by a Ca2+influx followed by a 40% loss of total taurine content accompanied by the loss of lesser amounts of other osmolytes. Kidney cells respond to a gradual change in osmolality by maintaining their volume at the initial level. This is termed isovolumetric regulation (IVR), which may activate regulatory processes other than those observed with sudden changes in osmolality. When cardiac myocytes were exposed to a gradual change in osmolality, they show a partial IVR which is not dependent upon extracellular Ca2+. Potassium channel blockers, quinidine and Ba2+, and the chloride channel blocker, diphenylamine-2-carboxylate (DPC), compromise IVR in our model. Tritiated taurine loss and total intracellular K+contents were analyzed in cultured cardiomyocytes submitted to a gradual change in osmolality. The cultured cells lost approximately 10% of their taurine and 35% of their total K+. These findings suggest that different compensatory mechanisms are activated when cells are exposed to stepwise and gradual changes in osmolality. Inorganic osmolytes (through conductive pathways) are preferentially mobilized during the physiological and/or patho-physiological IVR situation, perhaps reflecting energetic conservation in response to a less traumatic event for the cardiac myocytes.