Inhibitors of SERCA (sarcoplasmic/endoplasmic reticulum Ca(2+)-dependent ATPase) calcium pumps were used to investigate the involvement of internal Ca2+ stores in the GTP response in Paramecium. External application of these inhibitors was found to dramatically alter the typical behavioral and electrophysiological responses of Paramecium to extracellular chemical stimulation. In particular, 2,5-di-tert-butylhydroquinone (BHQ) strongly inhibited the backward swimming response of paramecia to externally applied GTP, though it did not inhibit the associated whirling response. BHQ also prolonged the normally brief electro-physiological response of these cells to GTP. BHQ completely blocked the behavioral and electrophysiological responses of Paramecium to extracellular Ba2+, but had no measurable effect on the behavioral or electrophysiological responses of these cells to another depolarizing stimulus, elevated external K+ concentration. These results suggest the involvement of nonciliary Ca2+ ions in the GTP and Ba2+ responses.