The present study assesses the modulatory potential of Chlorella vulgaris (E-25) on murine skin papillomagenesis, and the role of xenobiotic detoxication system in modulating the papillomagenesis pattern. Topical application of E-25 (500 mg/kg b.w./day) during peri-, post- or peri- and post-initiational stages of 7,12-dimethylbenz [a] anthracene (DMBA)-induced papillomagenesis, significantly modulated the a) tumor burden to 5.00, 4.33 and 3.94 (positive control value: 5.88 b) cumulative number of papillomas to 90, 78 and 67 (positive control value: 106); and c) percent incidence of mice bearing papillomas to 94, 90 and 89 respectively (positive control value: 100). E-25 treatment alone or during peri-, post- or peri- and post-initiational stages significantly elevated the sulfhydryl (-SH) and glutathlone S-transferase (GST) levels in the liver and skin tissues. However, the levels of microsomal cytochrome b5 (Cyt. b5) and cytochrome P-450 (Cyt. P-450) were not appreciably modulated by the topical treatment of E-25. The results suggest the chemopreventive potential of E-25 during peri-, post- or peri- and post-initiational stages of murine skin papillomagenesis. The possible significance of xenobiotic detoxication system in modulating the papillomagenesis pattern is discussed.