The purpose of the present study was to investigate an association of the endothelial nitric oxide synthase (eNOS) gene polymorphism with asthma. eNOS intron4 variable number of tandem repeats (27 bp repeats) genotypes were determined in asthma patients and control subjects using microplate PCR. The Caucasian Asthma patients displayed three alleles while Caucasian controls displayed only two alleles. However, African Americans displayed all three alleles in both asthma patients and controls. African American controls displayed significantly higher a allele, significantly lower b allele, as well as c allele than those in Caucasians. This was the first report to show that there was a novel eNOS genotype present in asthmatic patients but not in control subjects in the Caucasian Community. The novel allele which we termed the c allele, could be a significant risk factor in the etiology of asthma in Caucasians. This novel allele could be involved in higher levels of NO in our Caucasian asthmatics.