Reports of systemic absorption of sunscreens prompted a study of the effects of emulsions of 3 commonly used sunscreens on cultured human cells; vegetable oil and paraffin oil were used as controls. Ethylhexyl p-methoxycinnamate (EHMC), octyl p-dimethylaminobenzoate (PABA) and oxybenzone (OB) inhibited cell growth and DNA synthesis and retarded cycle progression from G1 in the dose range 25-100 mu g/mL. An extended period of exposure (up to 24 h) was required for maximum uptake of sunscreens and for inhibition of cell growth. Melanocytes and fibroblasts tended to be more resistant than tumor cell lines (melanoma, cervical carcinoma), Sunscreens had no major effects on the transcription of certain genes, as judged by the activity of reporter constructs driven by the p53, c-fos and metal response (sheep metallothionein Ia promoter) elements and transfected into a human melanoma cell line (MM96L). The activity of the cytomegalovirus promoter was also not affected. A cell line (CI80-13S) with mitochondrial dysfunction was significantly more sensitive to growth inhibition by EHMC and PABA than the other cell lines tested. Treatment of MM96L with the mitochondrial inhibitor ethidium bromide sensitized the cells to killing by cotreatment with sunscreens, in association with increased cellular uptake of ethidium bromide, These results established conditions for studying the action of sunscreens on cultured human cells. Further studies are required to determine whether the mitochondrial stress and changes in drug uptake associated with sunscreens in the above cell lines are relevant to their action in vivo.