There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case -control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend 40.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR ¼ 2.68, P ¼ 0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR ¼ 4.74, P ¼ 0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (Po0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers. There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer. Many proven carcinogens are present in tobacco and tobacco smoke (Hecht, 1999;Hoffmann and Hoffmann, 1997). Tobacco-related compounds have also been detected in human placenta, fetal blood, urine of offspring and in breast milk of smoking mothers (Perlman and Dannenberg, 1942;Everson et al, 1986Everson et al, , 1988Woodward et al, 1986;Hansen et al, 1992;Myers et al, 1996;Pinorini-Godly and Myers, 1996;Arnould et al, 1997;Daube et al, 1997).Previous case -control studies have tended to show weak associations between maternal cigarette smoking during pregnancy and childhood cancers (IARC, 1986;Severson et al, 1993;Tredaniel et al, 1994;Sorahan et al, 1995Sorahan et al, , 1997a Sorahan et al, , b, 2001Klebanoff et al, 1996;Shu et al, 1996). There is somewhat stronger and more consistent evidence for a paternal preconceptional effect, although relative risks in most case -control studies are only just above one (Severson et al, 1993;Shu et al, 1996;Ji et al, 1997;Sorahan et al, 1997b;. This effect has been attributed to germ-cell mutations during spermatogenesis caused by tobacco products (Wyrobeck, 1993;Wyrobek and Adler, 1996;Woodall and Ames, 1997). Relevant studies are reviewed by Thornton and Lee (1998).The United Kingdom Childhood Cancer Study (UKCCS) is a nationwide population-based...