Psoralen photochemotherapy (PUVA) is widely used in the treatment of psoriasis. Some therapy regimen have been associated with increased risk of skin cancer. Free radical species are thought to play a role in psoralen phototoxicity and photocarcinogenesis. It has been reported that the antioxidant butylated hydroxytoluene (BHT) inhibits acute phototoxicity by PUVA but does not reduce therapeutic efficacy. It has also been shown that BHT inhibits UVB-induced erythema, tumorigenesis and induction of ornithine decarboxylase (ODC) activity--ODC activity is thought by some to be associated with tumor promotion. Therefore, we have investigated the effect of BHT on psoralen tumorigenesis and PUVA-induced epidermal ODC activity. SKH-Hr-1 hairless albino mice were treated with topically applied 8-MOP and exposed to UVA (3X weekly) for 31 weeks with and without BHT administered either in the diet or topically. Induction of ODC activity was determined in similar experimental groups 24 h after a single exposure to UVA. Neither route of BHT administration had any effect on 8-MOP phototumorigenesis. However, BHT when administered in the diet reduced induction of ODC activity by 40% (p less than 0.05). These data indicate different mechanisms for UVB- and PUVA-induced carcinogenesis and again bring into question the relationship between induction of ODC activity and photocarcinogenesis.