A few hundred hybridoma cell lines derived from spleen cells of normal, nonimmunized, 6-day-old BALB/c or BALB.B10 mice were screened for H- and L-chain production. Roughly half of these hybridomas produced no Ig chain into the culture supernatants. Of the Ig-secretors, 80% produced IgM molecules carrying either kappa or lambda chains in a ratio of 9:1. A surprisingly high frequency of clones (roughly 20%) were found to produce only light chains and in this group, the kappa/lambda ratio was altered to around 1. The indications from the primary screening were confirmed by isolating a large number of these hybrid cell lines and extensive testing of both culture supernatants and ascitic fluids in solid phase RIA and ELISA assays. In some cases, the absence or presence of heavy chain synthesis and the isotype of the light chain was also confirmed by biosynthetic labeling of the hybridoma clones, specific immuno-precipitation of cell lysates or supernatants, followed by analysis in SDS polyacrylamide gels. We conclude from these results that the absence of heavy chain expression is accompanied by frequencies of lambda chain expression, which are much higher than those observed in normal immunoglobulin producing cells, and equal to those of kappa chains. This conclusion can be interpreted as to suggest that the low frequency of lambda producing cells in mouse is in part determined by restrictions in the heavy-light chain interactions at the protein level.(ABSTRACT TRUNCATED AT 250 WORDS)