Mechanism of Ca2+ mobilization from caffeine- and inositol-1,4,5-trisphosphate (IPA3) -sensitive internal Ca2+ stores were studied in embryonic chick sensory neurones. Caffeine transiently increased [Ca]i in one-quarter of all cells tested. For non-responsive cells caffeine elicited [Ca]i transients at elevated [Ca]i level indicating the operation of Ca2+-induced Ca2+ release. Injections of IP3 and GTPγ S-induced [Ca]i transients but IP3mobilizing agonists, carbachol and bradykinin, were either ineffective or produced weak responses. Pre-treatment with staurosporine and H-7 increased both the peak [Ca]i and the percentage of cells responsive to agonists. The effects were abolished by phorbol esters indicating that down-modulation is mediated by protein kinase C.