Expression of cyclin D1 is believed to lead to progression through the G1-S cell cycle checkpoint, and both experimental and pathological evidence suggest that over-expression of this protein may increase the risk of several cancers, including transition cell carcinoma of the bladder. Two major transcripts have been described for CCND1, the gene encoding cyclin D1. CCND1 870A-->G, a common single nucleotide polymorphism in the splice donor region of exon 4, may modulate expression of these transcripts, with the A variant resulting in an increased pool of the isozyme encoded by transcript form b. A statistically significant 1.8-fold increased risk for bladder cancer among individuals possessing the A/A genotype was recently reported in a hospital-based case-control study conducted among native Japanese. We conducted a population-based case-control study of incidence of bladder cancer among non-Hispanic whites in Los Angeles County to examine the relationship between CCND1 870A-->G genotypes and bladder cancer risk. No association between the A/A genotype and risk was observed (odds ratio = 0.90, 95% confidence interval 0.60-1.33). The null association was not appreciably modified by bladder cancer risk factors, including lifetime smoking history, or by histopathologic classification.