Objectives. Phlebotomists occupationally exposed to isopropanol (IPA) (2-propanol) and naïve controls (n = 12 per group) were exposed to the time-weighted average threshold limit value of 400 p.p.m. IPA for 4 h in an environmental chamber to investigate: (i) acute effects of sensory irritation using subjective health symptom reports and objective, physiological end-points; and (ii) differences in measured effects in relation to exposure history. Methods. Before, during and after exposure subjects gave self-reports of health complaints. During exposure subjects rated the intensity of the odor, sensory irritation and annoyance. Objective end-points of ocular hyperemia, nasal congestion, nasal secretion and respiration were obtained at various times before, during and after exposure. Results were compared with exposure to phenylethyl alcohol (PEA), a negative control for irritation, and to clean air (CA), a negative control for odor and irritation, using a within-subjects design. Results. Significantly higher intensity ratings of odor, irritation and annoyance were reported during the exposure to IPA, when compared with exposure to CA or PEA. Nevertheless, the overall level of reported sensory irritation to IPA was low and perceived as ‘weak’ on average. Health symptom ratings were not significantly elevated for IPA as compared with PEA or CA exposure. The only physiological end-point that showed a change exclusively in the IPA condition was respiration frequency: relative to baseline, respiration frequency increased in response to IPA in both groups. No differences were encountered between the occupationally exposed and the control groups. Conclusions. The increase in respiration frequency in response to IPA may reflect either a reflexive change due to sensory irritation (an autonomic event) or a voluntary change in breathing in response to perception of an unpleasant, solvent-like odor (a physiological event caused by cognitive mediation). Our findings on objective end-points, including nasal and ocular sensory irritation, did not confirm subjective irritation reports. Irritation reports and odor intensity decreased, rather than increased, over time, lending credence to the cognitive argument and suggesting that the elevated subjective responses to IPA may be mediated by responses to its odor.