Sphingolipids comprise a very important class of second messengers involved in cell growth, differentiation, and apoptosis, among other different functions. Recently, these lipids have been implicated in calcium mobilization in different cell lines, including Jurkat T-lymphocytes. However, the effect of each particular sphingolipid appears to be cell-line specific. Among them, the least studied is ceramide-1-P (Cer-1-P). Here, we show that Cer-1-P increased the intracellular Ca2+ concentration in Jurkat T-cells. Furthermore, laser-scanning confocal microscopy indicated that Ca2+ is released from the endoplasmic reticulum. An effect on store-operated Ca2+ channels was evidenced by whole-cell "patch clamp" measurements after Cer-1-P induced Ca2+ store depletion. The mechanism of action of Cer-1-P resembles that of the Jurkat anti-TCR antibody, but differs from that of ceramide, since Cer-1-P induced an increase in Ins(1,4,5)-P-3. (c) 2005 Elsevier Inc. All rights reserved.