In chronic myeloid leukemia (CML), experimental studies using synthetic peptides identical to the bcr-abl fusion region have revealed the capability of specific peptides to bind to human leukocyte antigen (HLA) class I molecules (HLA-A2, A3, A11, B8) and class II molecules (HLA-DR1, DR2, DR3, DR4 and DR11). Individuals expressing HLA-A3, B8 or DR4 have a diminished risk for the development of CML in Caucasian populations. A statistically significant increase in the frequency of Cw3 and Cw4 antigens in Caucasians and European CML patients has been reported. However, HLA associations in CML have not been reported in India. In lieu of the allelic diversity of HLA in the Indian population, the present study assessed the possibility of an association of HLA molecules in Indian patients with CML. HLA A, B, C and DRB1 antigen associations in 180 clinically diagnosed Indian CML patients (aged 17 - 54 years) were analysed and compared with age-matched (n = 100) healthy individuals from the same ethnic background. In the HLA class I antigen distribution, a significant decrease was observed in HLA-A11 (25.6% versus 39%; P = 0.027, odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.31 - 0.94) and HLA-Cw6 (7.8% versus 20%; P = 0.005, OR = 0.34, 95% CI = 0.15 - 0.74). Among the DRB1 alleles, HLA-DRB1*13 (7.8% versus 17%; P = 0.031, OR = 0.41, 95% CI = 0.18 - 0.93) was decreased in CML patients. However, the differences for HLA-A11 (P(c) = 0.351) and DRB1*13 (P(c) = 0.403) did not remain significant after the application of a correction factor for the P-value. These results suggest that the development of CML is apparently associated with HLA phenotypes specific to each population and indicate that expression of HLA-Cw6 may result in a protective effect on CML acquisition in the Indian population.