Changes in cardiac gene expression were studied during development and regression of cardiac hypertrophy in spontaneously hypertensive rats (SHR) in an attempt to determine some of the biochemical factors responsible for alterations in cardiac mass. Chronic nifedipine treatment of SHR (30 mg/kg per day for 20 weeks) led to a marked reduction in arterial blood pressure and to a subsequent regression of cardiac hypertrophy. Cardiac mRNA concentration decreased, whereas cardiac protein concentration remained unchanged. Changes in cardiac gene expression, as reflected by the decrease in cardiac mRNA concentration, were thus identified as a major factor responsible for the regression of cardiac hypertrophy after nifedipine therapy of SHR.