To examine the possible associations between CCR5delta32 and asthma and related phenotypes in high-risk families.A total of 154 families (453 individuals), with at least two affected children with physician-diagnosed asthma (PDA) and atopy defined as one or more skin prick test to common inhaled allergen (SPT wheal > or = 3 mm), were studied. Samples were genotyped using PCR assay and tested for possible associations by TDT and PDT and case control analyses.Overall allelic frequency for CCR5delta32 was 26.1%, and both TDT and PDT demonstrated similar nonsignificant associations (p=0.123) and (p=0.088). Analysis by the clinical categories of non atopic and atopic asthma and presence or absence of atopy without asthma failed to identify any significant associations. However there were strong associations of the mutant allele with the phenotypes of negative SPT, PC 20 less than 8 mg/ml, baseline FEV1 greater than the population median (83.5% predicted) and serum IgE less than 100 IU/l for child probands but only for negative SPT in unrelated parents.Non-significant association was seen with family based association tests (FBATs). The strong associations with the asthma related phenotypes in child probands support previous observations that CCR5 is in linkage disequilibrium with CCR2 or CCR3.