We investigated the protective effects of commercial sunscreening agents against UVB-induced photoresponses in group A xeroderma pigmentosum (XPA) model mice. XPA gene-deficient mice are defective in nucleotide excision repair and show a high incidence of skin tumors and severe acute inflammation in response to UVB irradiation, in a similar manner to XP patients. SPF 10 and SPF 60 sunscreens protected partially and almost completely, respectively, ear swelling responses produced by UVB up to 200 mJ/cm2 in (-/-) mice. XPA (-/-) mice were irradiated three times a week to a cumulative dose of 2.6 J/cm2 UVB for a period of 24 weeks with or without SPF 10 or SPF 60 sunscreen. UV-induced skin tumors had developed in all unprotected (-/-) mice (13.3 tumors per mouse) at the completion of UVB irradiation. The SPF 60 sunscreen afforded stronger protection against photocarcinogenesis (1.0 tumors per mouse) than the SPF 10 sunscreen (4.4 tumors per mouse). Regarding photoaging, SPF 60 sunscreen also protected against mast cell infiltration (79% inhibition), elastic fiber accumulation, and dermal cyst proliferation in XPA (-/-) mice compared with unprotected (-/-) mice. In (-/-) mice, the SPF 60 sunscreen provided stronger protection against cyclobutane pyrimidine dimer formation shown immunohistologically following irradiation with 200 mJ/cm2 UVB than the SPF 10 sunscreen. The XPA model mouse is a useful animal for the evaluation of the photoprotective ability of sunscreens because photoresponses, even chronic changes, can be easily and quickly induced experimentally.