The association between HLA homozygosity and measles-specific Th(1) (IFN-gamma, IL-2 and IL-12p40) and Th(2) (IL-4 and IL-10) cytokine responses were assessed in a group of 339 healthy schoolchildren 12-18 years of age previously immunized with two doses of live-attenuated measles virus vaccine. No associations were observed between class I HLA homozygosity and measles-specific cytokine levels. Children who were homozygous at the class II DRB1, DQA1, DPA1 and DPB1 loci had higher median IFN-gamma secretion levels compared with children who were heterozygous for DRB1 (77.7 vs. 39.5 pg/ml, p=0.05), DQA1 (60.9 vs. 36.6 pg/ml, p=0.03), DPA1 (46.1 vs. 27.1 pg/ml, p=0.01) and DPB1 (61.5 vs. 36.0 pg/ml, p=0.01) loci, respectively. Homozygosity at increasing numbers of HLA loci ( >or=4) was associated with increased IFN-gamma secretion levels (test for trend p-value=0.01). Our results suggest that HLA homozygosity showed no disadvantage for measles-specific cytokine responses and instead was associated with increased IFN-gamma levels.