Five cell lines (one parental, two transformed melanin producing, and two transformed non‐melanin producing) were evaluated for the responses to 2‐ and 4‐hydroxyanisole (2HA, 4HA) alone or combined with hyperthermia or radiation. All cells exhibited a non‐specific toxic response to the two compounds and the effect was exposure time and concentration dependent and was greater for 4HA compared to 2HA. In addition, the two melanin‐producing cell lines were more sensitive, demonstrating specific toxicity to such cell lines. The treatment with either 2HAor4HA combined with heat and radiation resulted mostly in additive or antagonistic effects, except for one combination of 2HA plus radiation in the melanin‐producing R25 cells. Thus, while these compounds may be useful in therapy for pigmented melanomas, combined treatment with radiation is not