Ultraviolet (UV) radiation is considered to be essential for the progression of actinic keratosis (AK) to squamous cell carcinoma (SCC); however, the mechanisms have not been fully elucidated. To understand this process, the effects of UV radiation on the transforming growth factor beta 1 (TGF beta 1)/Smads pathway and p53 in normal skin and AK were studied. Normal human skin and AK tissues were cultured and divided into the following four groups according to the UV radiation dose: 0 (control group), 5, 10, and 20 J/cm(2). The tissues were radiated for four consecutive days; 24 h after radiation, the tissues were collected for investigation. Compared with the control group, greater proliferative inhibition and apoptosis were induced by UV radiation in normal skin than AK. The expression of TGF beta 1, Smad7, and p53 was increased in AK and normal skin, while the level of T beta RII was decreased. Smad2 was reduced in AK only. The expressions of T beta RI, Smad3, and Smad4 were not significantly changed. The results demonstrated that although p53 was induced, suppression of the TGF beta 1/Smads pathway by UV radiation might contribute to the progression of AK to SCC.