Polymorphisms in the TNF-alpha (A-308G), IL-4 (C-589T), and Fcalpha RIbeta (E237G) genes have been associated with asthma and related phenotypes. To determine the predictive value of these polymorphisms we have assessed their relative risk (RR) for the development of atopy, asthma, and rhinitis in a high-risk infant population that is being followed longitudinally from birth. DNA was extracted and genotyped for 373 infants and 572 parents for each polymorphism. Phenotypic data were collected for atopy and allergic diseases in the infants at 12 mo of age. The prevalence of these phenotypes in the 281 white infants was compared in each genotypic group. There were no differences in the prevalence of any phenotype between genotypes of the TNF-alpha and Fcalpha RIbeta polymorphisms. However, we found that the IL4-589*T allele was associated with "probable" asthma (RR = 4.1) and that homozygotes for the IL4-589*T allele had an increased risk for the development of rhinitis (RR = 2.4). Using the transmission disequilibrium test, an association of IL4-589*T with atopy was found. We conclude that IL-4-589*T, but not TNF-alpha-308*2 or Fcalpha RIbeta*G, is a risk factor for the development of atopy, asthma, and rhinitis by 12 mo of age.