This retrospective study characterized the P300 component of the auditory event related potential (ERP) and assessed its diagnostic value in occupational chronic solvent encephalopathy (CSE). The P300 was recorded on 86 CSE patients by the classical oddball paradigm. In addition to the laboratory's reference values, we used an age and education matched control group that consisted of 104 blue-collar workers with no known occupational solvent exposure. The association of P300 values with solvent exposure indices, major depression, alcohol consumption, and neuropsychological parameters was studied. The P300 amplitude was lower in CSE patients (mean 7.5 microV; S.D. 3.6) compared to laboratory controls (mean 11.8 microV; S.D. 4.1; F(1,167)=24.4; p<0.001, 95% CI -4.4 to -1.8) and to matched controls (mean 9.0 microV; S.D. 4.0; p=0.007, 95% CI -2.6 to -0.4). The P300 latency was longer in the CSE patients (mean 358 ms; S.D. 28) compared to laboratory controls (mean 339 ms; S.D. 19, F(1,167)=7.6, p=0.006, 95% CI 3.12-18.7) but did not differ from matched controls (mean 358 ms; S.D. 22; p=0.947, 95% CI -7.4 to 6.9). The solvent exposure indices, major depression, or alcohol consumption did not associate with the P300 values. The P300 amplitude correlated positively with the Digit Symbol test. All the amplitude values in the patient group and in the matched control group were classified as normal (i.e. age corrected mean+/-2.5S.D.) against the laboratory's reference values. Thirty percent of the latencies in the CSE patient group and 26% in the matched control group were classified as abnormal. At group level, the decreased P300 amplitudes in CSE patients may reflect solvent-related pathophysiology. However, the P300 measured with the classical oddball paradigm does not seem to be sensitive at individual level or useful in clinical practice.