CC chemokine receptor (CCR)-3 is a seven-transmembrane-spanning G-protein-coupled receptor (GPCR) that is involved in the recruitment of inflammatory cells in allergic responses and acts as a co-receptor for entry of HIV into cells. Selected polymorphisms in GPCRs have been shown to have dramatic effects on the manifestation and/or susceptibility to a variety of diseases. In this report, we tested whether the human CCR-3 gene locus is genetically polymorphic. Using single-stranded conformational polymorphism analysis of genomic DNA, the CCR-3 gene is shown to contain four nucleotide polymorphisms with allele frequencies ranging from 0.005 to 0.13. Two polymorphisms encode for an amino acid change. One of these polymorphisms encodes for a non-conservative change of arginine to glutamine at position 275 of the third extracellular loop. Stratification of the DNA samples into a population with asthma suggested no change in this allele's frequency. Another polymorphism encodes for a leucine to proline substitution in the intracellular cytoplasmic tail of CCR-3. The most frequent polymorphism, T51C, occurs in 26% of individuals and encodes for a silent substitution. Thus, CCR-3 contains several genetic variations which may have consequences in disease processes that involve this receptor.