Complete suppression of expression of immunoglobulin K light chain was achieved by injecting female mice from birth with a mixture of antisera against the jz heavy chain and K light chain (anti-AL and anti-K). Then their offspring were injected with anti-K from birth. This resulted in stable suppression as long as anti-K injections were continued. K light chain was not detectable either in serum or at the cellular level. The number of B cells in spleen and the concentration of immunoglobulin classes and subclasses in serum were normal. The normal levels were achieved by a compensating enhancement of A light chain expression. Analysis of the light chains of immunoglobulins secreted by spleen cells from suppressed mice after liposaccharide stimulation by two-dimensional gels showed A chain to have a limited heterogeneity. Primary responses to dinitrophenol, influenza strain A, and keyhole limpet hemocyanin were drastically affected, whereas secondary responses appeared to be quite normal, suggesting a surprisingly large potential repertoire.Two types of immunoglobulin light chains, K and X, are present in mammals and birds (1, 2). The reason for the parallel existence of two light chain types is unclear, especially because some species show a remarkable imbalance towards one or the other. In the horse, for example, X light chains are carried by about 95% of serum immunoglobulins (2), whereas in the mouse X light chains constitute only 2-5% of the serum light chain pool (2, 3). From sequence data of mouse myeloma proteins, it was concluded that this imbalance is a reflection of the number of germ-line genes for the variable (V) part of the particular light chain (4). Indeed, current estimates on the number of germ-line genes based on analysis at the DNA level are 100-200 V genes for K (VK) and two for X (VA) (5-7).The relative contribution of the two classes of light chain to the immune response can be evaluated in mice that ex-press only one type of light chain. The loss of X chain seems to have no drastic effects because SJL and BSVS mice, which display a lower expression-1/50th-of X chain than do other mouse strains (3,8,9), are not noticeably immune deficient.The effect of a loss of expression of K chain should be more drastic, given its major contribution (>90%) to the normal repertoire. The immune deficit due to loss of expression of K chain would be expected to depend upon the number of germ-line VA genes that the animal expresses. In the rabbit (normal level of K chain, 90-95%; refs. 2, 10), a strain exists that has lost the expression of the major K-type chain and whose immune system behaves quite normally (10). In this case it was shown that the V region of X chain is encoded by multiple (>20) germ-line genes (11), and a second K chain locus is expressed in higher quantities than normal (12). Because in mice only two VA genes exist, the complete loss of the expression of K chain should result in visible holes in the repertoire.