Changes in cytosolic calcium are crucial for numerous processes including neuronal plasticity. This study investigates the regulation of cytosolic calcium by corticotropin-releasing factor (CRF) in midbrain dopamine neurons. The results demonstrate that CRF stimulates the release of intracellular calcium from stores through activation of adenylyl cyclase and PKA. Imaging and photolysis experiments showed that the calcium originated from dendrites and required both functional IP3 and ryanodine receptor channels. The elevation in cytosolic calcium potentiated calcium-sensitive potassium channels (sK) activated by action potentials and metabotropic Gq-coupled receptors for glutamate and acetylcholine. This increase in cytosolic calcium activated by postsynaptic Gs-coupled CRF receptors may represent a fundamental mechanism by which stress peptides and hormones can shape Gq-coupled receptor-mediated regulation of neuronal excitability and synaptic plasticity in dopamine neurons.