Experimental insertion of a retrovirus into the germ line of mice has resulted in an embryonic recessive lethal mutation. Integration of the proviral genome occurred at the 5' end of the alpha 1(I) collagen gene, leading to complete transcriptional block. Developmental arrest of embryos homozygous at the mutated allele coincides with high expression of the gene in normal embryogenesis. Insertion mutagenesis by retroviruses may offer a general approach to the identification and isolation of genes which are transcriptionally active during mammalian development.