Attempts to identify susceptibility loci that, on their own, have marginal main effects by use of gene-gene interaction tests have increased in popularity. The results obtained from analyses of epistasis are, however, difficult to interpret. Gene-gene interaction, albeit only marginally significant, has recently been reported for the interleukin-4 and interleukin-13 genes (IL4 and IL13) with the interleukin-4 receptor A gene (IL4RA), contributing to the susceptibility of type 1 diabetes (T1D). We aimed to replicate these findings by genotyping both large family and case-control data sets and by using previously published data. Gene-gene interaction tests were performed using linear regression models in cases only. We did not find any single-locus associations with T1D and did not obtain evidence of gene-gene interaction. Additional support from independent samples will be even more important in the study of gene-gene interactions and other subgroup analyses.