Nerve growth factor (NGF) treatment converts rapidly dividing PC12 cells into a neuronal phenotype. To understand the Ca2+ sequestration mechanisms accompanying this differentiation, we examined the endoplasmic reticulum Ca2+ (SERCA) pump levels using two different assays: ATP-dependent azide insensitive oxalate stimulated 45Ca2+ uptake by PC12 cells permeabilized with saponin, and Western blots using a monoclonal antibody which reacts with all the SERCA isoforms. We also examined the reaction to an antibody against the plasma membrane Ca2+ (PMCA) pump. NGF treatment decreased the SERCA pump expression but it increased the PMCA pump level. These results are consistent with a greater role of PMCA pumps in neuronal cells than in most other cells and with an increased role of SERCA pumps during cell proliferation.