Cytochrome P450 2D6 (CYP2D6) codes for a phase I enzyme that is responsible for the biotransformation of a range of chemicals. Studies investigating the role of CYP2D6 and the risk of Parkinson's disease (PD), alone and in conjunction with environmental exposures, are contradictory. We used data from the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS) to investigate the association between CYP2D6 HhaI polymorphism in exon 6, various occupational exposures (e.g. metals, pesticides, chemicals) and the risk of PD. HHP/HAAS is a longitudinal cohort study begun in 1965 designed to evaluate heart disease, stroke, and later dementia in 8,006 Japanese-American men aged 45-68. Occupational exposure was independently assessed by three industrial hygienists who determined likelihood of exposures for each participant's usual occupation. Genotyping data was available for 75 incident cases of PD (mean age at baseline 54.4; standard deviation (SD) 5.1) identified through deat certificate, medical record review, and medical examination. A total of 127 controls without PD were frequency matched by age (mean age at baseline 54.4; SD=5.3) to the case group. No association was observed between CYP2D6 HhaI polymorphism and PD in this population (Odds Ratio (OR) = 0.8; 95% Confidence Interval (CI)= 0.4, 1.4), nor was PD found to be associated with occupational exposures to solvents or pesticides either independently or in the presence of CYP2D6 (p>0.05). However, PD cases were two times more likely to have occupational exposure to metals than the controls (OR=2.2; 95% CI=1.2, 4.0). This association did not change in the presence or absence of CYP2D6. In conclusion, we found that among the Asian-Americans in the HHP/HAAS study CYP2D6 HhaI polymorphism in exon 6 was not associated with PD, nor was there evidence of an interaction between this gene and an occupational exposure (p>0.05). Our findings did however indicate that occupational exposure to metals may be associated with PD. This finding warrants further follow-up.