The site-directed recombinase Cre can be employed to delete or assemble genes in the genome of living cells. We have constructed expression vectors for chimeric Cre recombinases carrying a mutated hormone binding domain either at the C-terminus only (CreMer) or at both the N and C-termini (MerCreMer). The chimeric Cre proteins can be activated by culturing transfected cells with 4-hydroxytamoxifen. In transfected embryonic stem (ES) cells, we compared the extent of recombination of a floxed gene with the expression levels of the chimeric Cre proteins. Our data demonstrate that the bulky MerCreMer protein is not less active than the CreMer protein. Thus, the tighter control and low background activity of the MerCreMer enzyme is not due to a generally low recombinase efficiency.