In order to examine if cardiac hypertrophy is associated with changes in -adrenoceptor signal transduction mechanisms, pressure overload (PO) and volume overload (VO) were induced in rats by occluding abdominal aorta and creating aortocaval shunt for 4 and 24 weeks, respectively. After hemodynamic assessment of the animals, the left ventricle particulate fraction was isolated for the measurement of ₁-adrenoceptors and adenylyl cyclase activity whereas cardiomyocytes were isolated for monitoring the intracellular concentration of Ca²⁺ ([Ca²⁺]_i). Although both PO and VO produced cardiac hypertrophy and increased the left ventricular end diastolic pressure (LVEDP) at 4 weeks, cardiac function was increased in PO animals but remained unaltered due to VO. On the other hand, cardiac hypertrophy and increased LVEDP were associated with depressed cardiac function at 24 weeks of inducing PO or VO but clinical signs of congestive heart failure were evident only in animals subjected to VO. Isoproterenol-induced increases in cardiac function, activation of adenylyl cyclase activity and increase in [Ca²⁺]_i as well as ₁-adrenoceptor density were unaltered due to PO at 4 weeks, augmented due to VO at 4 weeks and attenuated due to both PO and VO at 24 weeks. These results suggest that alterations in 1-adrenoceptor signal transduction are dependent upon the type and stage of cardiac hypertrophy.