IL4, the gene coding the prototypic Th2 cytokine, has been frequently studied in the context of several inflammatory conditions, but conclusive results have not been obtained. This gene is located in the 5q31–33 complex genetic region, which shows some susceptibility factors to type 1 diabetes (T1D) and rheumatoid arthritis (RA) among other inflammatory conditions. Our aim was to assess the involvement on T1D and RA of IL4 polymorphisms considered individually and in combination with other polymorphisms in 5q31–33, specifically in the OCTN locus, where the L503F polymorphism has been associated with Crohn’s disease and other Th1 diseases. We performed a case-control study including 316 T1D patients, 599 RA patients and 540 healthy controls, all of them corresponding to white Spanish individuals. The IL4 single-nucleotide polymorphisms (SNPs) −590C/T (rs2243250) and the OCTN1 exonic SNP L503F (rs1050152) were analysed in all samples. Frequency comparisons of −590C/T and stratified analysis including both cited SNPs were performed using chi-square tests. The −590C/T IL4 SNP was not found associated with T1D or RA when individual analyses were performed. However, a significant association with T1D emerged after stratification by L503F [p = 0.02, odds ratio = 1.95, 95% CI = 1.07–3.55]. The location of the IL4 gene in the complex 5q31–33 genetic region, which contains many genes involved in immunological responses and presents linkage disequilibrium extended along many kilobases, makes necessary to interpret cautiously the previous IL4-association studies.