Several studies have shown that changes in behavior including, smoking cessation, and modifications in overall dietary pattern can modulate various biomarkers, such as circulating homocysteine and carotenoid concentrations. Results from laboratory studies suggest that increased carotenoid concentrations exhibit anti-carcinogenic properties, while elevated homocysteine concentrations have been associated with increased cardiovascular disease risk. We have examined changes in diet, as well as plasma concentrations of a-carotene, b-carotene, lycopene, lutein, and b-cryptoxanthin in women enrolled in a randomized clinical trial, the Women's Healthy Eating and Living [WHEL] Study. The WHEL Study is investigating the effects of a high vegetable, fruit, fiber and low fat diet on breast cancer recurrence. Results from the pilot study of the WHEL clinical trial revealed that the intervention group had significantly higher vegetable and fruit servings and fiber at 12 months and significantly higher vegetable servings at 36 months compared to the control group (p < 0.05). Energy intake from fat was significantly lower in the intervention group at 12 and 36 months. At 36 months, the intervention group had significantly higher plasma concentrations of a-carotene and b-carotene compared to the control group. Repeated measures ANOVA revealed that the intervention group had significantly increased (p < 0.05 with Bonferonni correction) plasma b-carotene, a-carotene, lutein, and lycopene concentrations at 12 months and 36 months compared with baseline. Additionally, we examined whether the matrix (i.e. vegetable juice vs raw or cooked vegetables) in which vegetables are consumed influences serum carotenoid response. The results showed that serum concentrations of a-carotene and lutein were significantly higher in the vegetable juice group than in the raw or cooked vegetable juice group (p < 0.05). Recently, we analyzed plasma homocysteine concentrations in a subset of smokers matched on age and folate consumption to non-smokers in the main WHEL clinical trial. Preliminary data suggests that circulating homocysteine concentrations were not significantly different between smokers and non-smokers at baseline and 12-month. However, smokers, as well as non-smokers did significantly reduce (p < 0.05) plasma homocysteine concentrations from baseline to 12-month. These findings suggest that biomarkers, associated with cancer and cardiovascular disease risk, can be indicators of long-term fruit and vegetable intake, and be responsive to dietary and other lifestyle changes.