Chronic lymphocytic leukemia (CLL) is rare in Asians living in Asia and possibly in US Asians. In contrast, CLL is the most common leukemia in whites. The basis for this ethnic and geographic variation is unknown. We compared average annual age-adjusted incidence rates (AAIR) of CLL diagnosed from 1972 to 1995 among Los Angeles County-resident Asians, non-Spanish-surnamed- and Spanish-surnamed whites (non-Hispanic and Hispanic-whites) and blacks using the University Southern California-Cancer Surveillance Program (USC-CSP), the population-based cancer registry for Los Angeles County. Asian groups studied included Chinese, Japanese, Filipinos and Koreans. Expected numbers of CLL cases were based on the age-adjusted incidence rates in non-Hispanic whites and compared to numbers of cases observed in Chinese, Japanese and Filipinos. Possible association of socioeconomic state (SES) was assessed using AAIRs with SES-specific denominators. In the absence of denominators by birthplace, the association of birthplace and CLL-incidence was evaluated using proportional odds ratios (POR). Los Angeles County Asian males and females had significantly lower AAIRs than non-Hispanic whites (males: AAIR=0.7 per 100000 population, 95% confidence interval (CI), 0.5-1.0 vs. 4.4, 95% CI, 4.3-4.6; and females: AAIR=0.5, 95% CI, 0.3-0.7 vs. 2.3, 95% CI, 2.2-2.4). Fewer Japanese Chinese and Filipinos were diagnosed with CLL than expected (P<0.01). There was no association of birthplace (POR=0.9, 95% CI, 0. 5-1.9) or SES on CLL-risk. CLL-risk was markedly lower in Los Angeles County Asians compared to non-Hispanic whites. Neither birthplace nor socioeconomic state accounted for this difference suggesting a role for genetic or other environmental factors in decreasing CLL-risk.