Oxidative stress plays an important role in carcinogenesis, but few epidemiologic studies have examined associations with risk of colorectal cancer. Relationships between serum levels of oxidized low-density lipoprotein (oxLDL) and oxLDL antibody (oLAB) and colorectal cancer risk were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 161 incidents and deaths from colorectal cancer were identified through 1999, and 395 controls were matched for gender, age, and study area. Measurements were taken of serum oxLDL levels in 119 cases and 316 controls and serum oLAB levels in 153 cases and 376 controls. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, were 1.55 (0.70-3.46), 1.90 (0.84-4.28), and 3.65 (1.50-8.92) for oxLDL (P(trend) = 0.004) and 0.98 (0.54-1.80), 0.75 (0.39-1.48), and 1.68 (0.90-3.13) for oLAB (P(trend) = 0.140). Further adjustment for serum total cholesterol and alpha-tocopherol did not materially change these associations. Odds ratio (95% confidence interval) of the highest quartile of serum oxLDL compared with the lowest quartile was 3.40 (1.09-10.58; P(trend) = 0.045). Analyses restricted to colon cancer cases and corresponding controls yielded similar relationships between serum oxLDL and oLAB levels and risk. In conclusion, higher levels of serum oxLDL may increase risk of colorectal cancer.