Abstract Ca2+ signaling plays an important role in the function of dendritic cells (DC), the specialized antigen-presenting cells of the immune system. Here we describe functional ryanodine receptor (RyR) Ca2+ release channels in murine, bone marrow-derived DC. RT-PCR analysis identified selective expression of the type 1 RyR, with higher levels detected in immature rather than mature DC. The RyR activators caffeine, FK506, ryanodine and 4-chloro-m-cresol mobilized Ca2+ in DC, and responses to 4-chloro-m-cresol were inhibited by dantrolene. Furthermore, activation of RyRs both inhibited subsequent inositol trisphosphate-mediated Ca2+ release and provoked store-operated Ca2+ entry, suggesting a functional interaction between these intracellular Ca2+ channels. Thus, the RyR1 channel may play an intrinsic role in Ca2+ signaling in DC.