Styrene is a widely used industrial solvent associated with acute neurotoxicity. To investigate the relationships between exposure, blood concentrations, and the appearance of neurotoxic effects, four healthy males were exposed to styrene concentrations of 5-200 ppm in four different exposure-time profiles. A digit recognition test and P300 event-related evoked potential were used to measure neurologic function. A physiologically based kinetic (PBK) model generated close predictions of measured styrene blood concentrations, in the range of 0.01-12 mg/L, from this and 21 previous studies. Simulated peak brain concentration, duration × average exposure, and peak exposure level were predictive of toxicity. Central nervous system effects were expected at a blood concentration near 2.4 mg/L. A standard of 20 ppm was expected to protect styrene-exposed workers from acute central nervous system toxicity under light work conditions.