Background and objectives: Recent family-based studies have revealed a linkage between human chromosome 5q31 and asthma, elevated serum IgE levels and airway hyperresponsiveness (AHR). Among the candidate genes in this region is the gene encoding IL-4. This gene could be a candidate gene for asthma. The aim of this prospective case-control study was to assess the frequency of polymorphisms in the IL-4 gene promoter among asthmatic patients from Taiwan. Methods: The study consisted of 167 patients with asthma and 111 healthy subjects. PCR amplification followed by Bsm F1 restriction digestion were used to assign genotypes at the IL-4 promoter C-589T locus. Pulmonary function tests, methacholine challenge tests, total IgE, specific IgE antibodies against common inhalant allergens and total eosinophil counts were assessed in asthmatic patients. Results: The T allele frequency for the C-589T IL-4 gene promoter in asthma patients was higher than for normal subjects (P < 0.0001). The frequency discrepancy was found to be even higher for asthmatic patients with severe AHR (P < 0.05). There were no significant differences for the T allele frequency among asthmatic patients with the various other phenotypes such as high versus normal total eosinophil, high versus normal total IgE and high versus normal levels of specific IgE against mite, cockroach or cat dander, or dog dander. Conclusions: Polymorphism in the promoter of the IL-4 gene is associated with asthma and is a disease modifier in terms of the severity of AHR.