The nature of spontaneous mutations in the lacI transgene of Big Blue mice was determined in selected tissues. The mutant frequencies ranged from 2.5 x 10(-5) to 7.1 x 10(-5) for liver, spleen, bladder, stomach, kidney, bone marrow, lung and skin. We also determined the DNA sequence alterations in the mutants recovered from these tissues. In all tissues the predominant class of mutations was G:C-->A:T transitions, most of which occurred at 5'-CpG-3' dinucleotide sequences. Bladder, kidney and skin display the highest contribution of G:C-->A:T transitions. The second most common class of mutations was G:C-->T:A transversions. All other base substitution classes contributed < 10% each. Of the non-substitution events, the loss of a single base pair was the most frequently occurring event (< 10%). The similarity of mutational spectra (in terms of kinds of mutations detected by the lacI transgenic system) in all tissues examined supports the idea that similar mutational pathways function in these tissues in the absence of chemical or physical stimulus.