Mammalian cells possessing osmosensors have long been described in brain and kidney. The genetic basis of the response to hyperosmotic stress has been well characterized in prokaryotes. In contrast, the genetic response of eukaryotic cells is poorly understood. Therefore we investigated the effect of hypertonic NaCl and sucrose solutions on the transcriptional activation of the immediate-early genes (IEGs) egr-1 and c-fos in isolated ventricular adult rat cardiomyocytes. We observed that even small increases in osmolarity to 315 +/- 5 mosmol/l and 370 +/- 8 mosmol/l by hypertonic NaCl solution resulted in dose-dependent induction of egr-1 (4-and 5-fold) and c-fos (3-and 4-fold), respectively. Hypertonic sucrose solution had the same effect on egr-1 and c-fos mRNA levels while increased sucrose concentration under isotonic conditions had no effect. Cardiomyocytes exposed to hypertonic media did not significantly shrink as shown by a cell length measurement. We conclude that isolated adult cardiomyocytes possess an osmoreceptor mechanism which is able to sense even slight changes in osmolarity and to translate these into a transcriptional response of the myocardial IEG program.