Cellular phototoxicity induced by UVA irradiation and its potential application to therapy has been reported. In the present study, the induction of apoptosis induced by beta-carotene and dimethyl tetrasulfide (Me(2)S(4)) assisted by UVA irradiation in HL-60 cells was assessed. beta-carotene assisted by UVA significantly decreased the cell viability and induced DNA fragmentation in HL-60 cells. Me(2)S(4) combined with beta-carotene and assisted by UVA significantly inhibited the cell viability, and enhanced the caspase-3 activity which was completely inhibited by N-acety-L-cysteine. beta-carotene was significantly degraded by UVA, but this was not accelerated by Me(2)S(4) in a cell culture system. The photodegradation products of beta-carotene prepared by UVA irradiation regardless of the addition of Me(2)S(4) showed lower cytotoxicity than beta-carotene itself in HL-60 cells. These results suggest that the ROS- and caspase-3-dependent apoptosis induced by beta-carotene and Me(2)S(4) assisted by UVA was due to a synergistic action rather than to the sole effect of the photodegradation products of beta-carotene in HL-60 cells.