The role of the Na+-Ca2+exchanger as a major determinant of cell Ca2+is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to electrically stimulated heart tubes from control mouse embryos or embryos with the Na+-Ca2+exchanger knocked out. We monitored effects of the drugs on Ca2+transients. Both drugs depress the Ca2+transients at low concentrations even in the absence of any Na+-Ca2+exchanger. KB-R7943 and SEA0400 are not completely specific and should be used with caution as Na+-Ca2+exchange inhibitors.