To test the behaviour of a mutant form of p53 in the presence and absence of wild-type p53 in vivo, we mated p53-deficient mice containing a p53 null allele to transgenic mice containing multiple copies of a mutant p53 gene (Val 135). Animals hemizygous for the endogenous wild-type p53 gene with the mutant transgene exhibited accelerated tumour development and an altered tumour spectrum compared to their non-transgenic counterparts. In contrast, transgenic and non-transgenic animals nullizygous for endogenous p53 developed tumours at the same rate. Thus, the mutant Val-135 p53 allele may act in vivo in a dominant negative manner in the presence of wild-type p53 but does not display gain of function activity in the absence of wild-type p53.