In an 8.4 kb region, containing the entire Tnf gene and the last coding exons of the Lta and Ltb genes, was deleted by cre mediated excision of sequence between loxP sites inserted within Lta and Ltb via homologous recombination. Partial coding regions of Lta and Ltb were left intact separated by a single loxP site. RT-PCR analysis of homozygous mutant splenocytes activated by concanavalin A indicated an absence of transcript from all three loci.