The chemokine (C-C motif) receptors (CCR) 2 and 5 are members of a large family of G protein-coupled receptors, playing important roles in asthma pathogenesis. Using standard sequencing techniques, a total of 15 single nucleotide and 8 insertion/deletion polymorphisms (DIPs) (5 novels) were identified in and around these two genes. None of the studied polymorphisms (N=7, selected on the basis on linkage disequilibrium) was associated with asthma in a case (N=315) - control (N=337) study and showed no evidence for non-random transmission to individuals with asthma/atopy in Indian pedigrees (n=235). However, multilocus haplotype analysis based on simulations yielded a P=0.00005 in the case-control study and a P=0.03 for the family-based association studies. Furthermore, rs3918356 and rs743660 polymorphisms in CCR2 were found to be associated with total serum IgE levels in both the study designs. Thus, our study supports a significant role for chemokine receptor polymorphisms in genetic susceptibility to asthma.