The acute effects of endotoxins and lipid A on two intracellular responses, inositol phosphate generation and superoxide production were analysed in the DMSO differentiated premyelocytic leukaemic HL-60 cell line. Short-term incubation (1-10 min) with Escherichia coli-type LPS, Salmonella-type LPS and Lipid A caused significant increases in cellular InsP1 and InsP3, compared with control cells (P less than 0.5-P less than 0.001). The Escherichia coli-type LPS released approximately twice the quantity of InsP3 compared with Salmonella-type LPS (P less than 0.001). Lipid A-dependent stimulation of InsP3 production was also detected. The rate of superoxide production increased 1-10 min after addition of both Escherichia coli- and Salmonella-type LPS and Lipid A. Endotoxins and Lipid A caused a dose-dependent increase in intracellular oxidative activity. The superoxide response showed less species dependence and a higher response to particulate lipid A compared with the inositol phosphate response.