The identification of a new protein, p73, with structural and functional similarities to p53 protein suggests that a family of p53-like proteins is likely to exist. This study investigated the status of p73 protein in the early stages of 7,12-dimethyl benz[a]anthracene (DMBA)-induced carcinogenesis. Outbred young (6-week-old) male Syrian golden hamsters (Mesocricatus auratus; 40 animals) were randomly divided into four equal groups: a 3-week DMBA-treated experimental group, a 6-week DMBA-treated experimental group, a mineral oil-treated control group, and a non-treated control group. Following this, a total of 80 specimens of pouch mucosa were obtained from the 40 animals in the four groups. Positive nuclear staining for p73 protein was randomly distributed throughout the whole epithelial layer of the DMBA-treated specimens and was absent in controls. Positive p73 staining was observed in 8 of the 20 (40%) 3-week, and 14 of the 20 (70%) 6-week DMBA-treated specimens. None of the 3-week DMBA-treated specimens revealed more than 25% p73-positive keratinocytes, but, in 12 (60%) of the 6-week-treated specimens, more than 25% of the keratinocytes examined were p73-positive. This suggests that the longer the DMBA painting period, the higher the proportion of p73-stained pouch keratinocytes. Furthermore, a p73-dependent mechanism may be associated with the early stages of oral carcinogenesis. Such a mechanism could be very important to an understanding of the participation of p73 in the development of oral squamous-cell carcinomas.