Using the Swedish Medical Birth Registry, information on 1,362,169 infants born during 1983-1996 was analyzed in order to investigate the relation between maternal smoking during pregnancy and infant head circumference at birth. Infants of smoking mothers were at an increased risk to have head circumference <32 cm, and the adjusted odds ratios (OR) with 95% confidence intervals (CI) for any smoking, smoking <10 cigarettes per day, and smoking >/=10 cigarettes per day were: 1.65 (1.62-1.68), 1.52 (1.48-1.56), and 1.86 (1.81-1.92), respectively. A highly significant association between small head circumference for gestational age and maternal smoking was also found (ORs (with 95% CI) were for any smoking, <10, and >/=10: 1.58 (1.55-1.61), 1.48 (1.45-1.51), and 1.74 (1.70-1.79), respectively). For both outcomes, the observed dose-response effects were highly significant (P<10(-6)). Even more alarming was the finding that given a certain level of growth retardation, infants of smoking mothers were at an increased risk of small head circumference for gestational age compared to infants of non-smoking mothers (OR (with 95% CI) for any smoking adjusted for 'percentage of expected birth weight': 1.08 (1.06-1.10)). Given the evidence that maternal smoking specifically affects head growth, until contradictory evidence has been found, it seems reasonable to assume that maternal smoking during pregnancy affects brain development negatively.