Kappa and lambda, the two types of immunoglobulin light (L) chains present in mammals, contribute differently to the L chain pool of each species. Here we show that the extreme preponderance of kappa in the mouse results from programmed sequential activation of the kappa and lambda loci. Activation--a prerequisite of rearrangement--was monitored by analyzing transcription of unrearranged J-C clusters. Upon in vitro differentiation of a rearrangement-deficient pro/pre-B line, germ-line transcripts of the lambda J-C clusters, that are newly described here, became detectable 2 days later than their counterparts of J-C kappa. Clear differences could also be observed in vivo: germ-line transcripts of kappa were already present in large B220+ CD25+ pre B-II cells whereas germ-line lambda transcripts first became detectable at the consecutive developmental stage of small B220+ CD25+ pre-B-II cells. This activation pattern was found to be identical in mice which can not rearrange kappa due to a targeted deletion or inactivation of kappa. This suggests that pre-B-II cells follow a hit-and-run mechanism of development which includes programmed transitions and differential activation of the L chain loci, i.e. kappa first, then lambda. Thus, privileged activation of kappa might be the decisive factor in setting the 10:1 ratio of kappa to lambda present in the mouse.