This study explored the effect of deltamethrin, a pesticide, on free Ca2+ concentration [Ca2+]i, viability, and apoptosis in Madin–Darby canine kidney (MDCK) canine renal tubular cells. Deltamethrin at concentrations between 10μM and 40μM evoked [Ca2+]i rises in a concentration-dependent manner. The Ca2+ entry was inhibited by nifedipine, econazole, phorbol 12-myristate 13-acetate, and SKF96365. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) in a Ca2+-free medium abolished deltamethrin-induced [Ca2+]i rise. Treatment with deltamethrin also abolished BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C (PLC) activity with U73122 abolished deltamethrin-evoked [Ca2+]i rise. Deltamethrin killed cells at 30–60μM in a concentration-dependent manner. The cytotoxic effect of deltamethrin was not reversed by prechelating cytosolic Ca2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid. Annexin V/propidium iodide staining data suggest that 30–50μM deltamethrin induced apoptosis. Together, in MDCK renal tubular cells, deltamethrin induced [Ca2+]i rises that involved Ca2+ entry through protein kinase C-mediated store-operated Ca2+ channels, and PLC-dependent Ca2+ release from the endoplasmic reticulum. Deltamethrin also induced Ca2+-independent cell death that might involve apoptosis.