Various HLA class I and II associations previously reported in childhood acute lymphoblastic leukemia (ALL) have been inconclusive, probably due to the disease heterogeneity. Epidemiological studies have also put forward the hypothesis that childhood ALL could be a rare outcome of a common infection. On this ground immunogenetic susceptibility provided to a certain degree by HLA genes, might be suspected. The aim of this preliminary study was to investigate the possible HLA associations in childhood ALL in a Greek population. The study group consisted of 60 Greek children (35 boys/25 girls, age range: 9 months to 14 years) diagnosed and treated in our Department. The study group was also subdivided according to immunophenotype and classical risk criteria. 47 out of 60 patients had common ALL (cALL). 39 patients(39/60) comprised the high-risk subgroup (HR-ALL). A group of 200 healthy blood donors of Greek origin was used as controls. HLA typing of all known HLA class I and class II alleles was performed by serological method using immunomagnetic beads and double fluorescence. HLA antigen frequencies were analyzed by x2 test with Yates correction. Relative risks (RR) were calculated by cross-ratio. The results showed: 1) In overall ALL: increased frequency of HLA-B39 (RR=2.7, p=0.025), HLA-B27 (RR=2.8, p<0.05), HLA-Cw2(RR=2.4, p<0.05), HLA-DQ1 (RR=2.1, p<0.05). Increased frequencies of DR2 and DR4 were also found without reaching statistically significant level. 2)In cALL: increased frequency of HLA-A32, HLA-B22, HLA-B27, HLA-Cw2 and HLA-DQ1, with p<0.05. 3) In HR-ALL: increased frequency of HLA-B39 (p=0.025), HLA-B27, HLA-Cw7, HLA-DR4 and HLA-DQ3, with p<0.05. Conclusions: - HLA moderately statistically significant associations were found in childhood ALL and in the subgroups of cALL and HR-ALL - Some previously reported HLA associations in other populations (Cw7, DR4, DQ1, DQ3) were also found in this study - Our findings indicate that HLA-associated susceptibility in ALL may be determined inde-pendently by more than one HLA loci (HLA-B, -Cw, -DR, and -DQ loci).