THE present study examined whether the synthetic glucocorticoid dexamethasone (DEX) can modulate voltage-gated Ca2+ channel (VGCC) activity, and as a consequence agonist-induced increases in cytosolic Ca2+, in cultured rat adrenal medullary chromaffin (RAMC) cells. Exposure to 1 μM DEX for 48 h significantly increased peak VGCC current (Δ +140%). DEX treatment also significantly potentiated the increases in cytosolic Ca2+ in response to submaximal stimulatory concentrations of KCl (Δ +64%) and nicotine (Δ +32%). The Ca2+ channel agonist BAY K-8644 increased both VGCC current (Δ+109%) and potentiated the KCl-stimulated increase in cytosolic Ca2+ (Δ+35%) to a comparable extent to that seen with DEX. These data suggest that DEX treatment increases VGCC activity, and that this increased Ca2+ influx leads to potentiation of agonist-induced increases in cytosolic Ca2+ in RAMC cells.