The role of inositol 1,4,5-trisphosphate (InsP3) in cardiac myocyte function is unclear and controversial. Although agonists that activate InsP3 generation are positive inotropic agents in the heart and have been implicated in various cardiac pathologies, it is unclear whether InsP3 is responsible for any of their effects. We have investigated the expression and function of InsP3 receptors (InsP3Rs) in neonatal rat ventricular myocytes, and adult rat ventricular and atrial cardiac myocytes. We find significant expression of InsP3Rs in each of these tissues, and can evoke responses consistent with the receptors being functional and having access to replete calcium stores. Significantly, the promiscuous calcium release from InsP3Rs means that they contribute significantly to spontaneous diastolic calcium transients in hormone-stimulated ventricular and atrial myocytes. In recent studies, we have been examining the putative contribution of InsP3Rs to hypertrophic growth. These experiments were performed using spontaneously contracting monolayers of primary cultures of neonatal ventricular rat myocytes (NRVM). NRVMs were prepared by collagenase digestion of cardiac ventricles isolated from 1–2 day old Wistar rat pups. Quantitation of atrial natriuretic factor (ANF) by immunofluorescence and real-time PCR, together with cell surface area were used as measures of hypertrophy. Our data demonstrate that InsP3- induced calcium release is required for the induction of hypertrophy downstream of Gq- coupled receptors or increased workload. Furthermore, InsP3-induced calcium release may represent a mechanism by which gene transcription can be isolated from the increases in cytosolic calcium that occur during every heart-beat.