We have employed a method based on the Cre-/oxP recombination system of bacteriophage Pl to generate a mouse strain in which the JH segments and the intron enhancer in the IgH locus are deleted. By analysis of immunoglobulin isotype switch recombination in heteroxygous mutant B cells activated by lipopolysaccharide plus interleukind, we show that, on the mutant chromosome, switch recombination at the u gene switch region is strongly suppressed, whereas the switch region of the yl gene is efficiently rearranged. These data demonstrate an independent control of switch recombination at individual switch regions and suggest that, in the process of switch recombination, the alignment of the recombining strands occurs independently of and probably after the introduction of double-strand breaks into the switch regions involved.