To investigate the role of increased cytoplasmic free calcium levels ([Ca](i)) in sulphur mustard-induced cellular toxicity, the [Ca](i) of human epidermal keratinocytes exposed to sulphur mustard concentrations between 50 and 800 mu M were measured. No early increase in [Ca](i) was observed during the first 20 min after application of the agent. Furthermore, at 3, 6 and 24 h after exposure to sulphur mustard, the [Ca](i) of sulphur mustard-exposed cells differed only slightly from that of control cells. However, sulphur-mustard exposed cells responded with a weaker rise of [Ca](i) upon stimulation with histamine and ATP than control cells. These results suggest that sulphur mustard can induce small increases in [Ca](i), which reflect abnormal cellular physiology rather than acute toxicity. In addition, it has been shown that sulphur mustard disturbs cellular Ca2+ signalling in human epidermal keratinocytes.