Objectives: As there are sonic suggestions that a family history of cancer or autoimmune disease might be associated with an increased risk of leukemia in children, we explored this possibility using data from a matched case-control study conducted by the Children's Cancer Group. Methods: We compared the family history of cancer and autoimmune diseases of 302 infant leukemia cases (diagnosed within the first 18 months of life) with that of 668 individually matched controls in the United States and Canada. Results: Although not significant, cancer history in parents was found to he associated with an elevated risk of infant leukemia (odds ratio [OR] = 1.4, 95 percent confidence interval [CI] = 0.6-3.6), predominantly acute myeloid leukemia (AML) (OR = 2.2, CI = 0.6-9.0). Cancer history among second-degree relatives was also related to a non-significantly elevated risk of AML. Family history of autoimmune diseases, on the other hand, was generally not found to be related to the risk of infant leukemia. Conclusion: This study provided no strong evidence that family history of cancer or autoimmune disease is a major risk factor for infant leukemia.