Objective: The objective of the study was to estimate risk of acute and chronic maternal diseases during pregnancy in the origin of neural-tube defects. Materials and methods: Mothers with neural-tube defect fetuses/newborns (the NTD group), controls without any congenital defects (the normal control group) and controls with other defects (the other CA control group) were compared in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Of 1,202 cases with neural tube defects, 559 (49.8%) and 229 (19.1%) had mothers with one or more acute and chronic diseases, respectively. Of 38,151 mothers in the normal control group 14,004 (36.7%) and 8,328 (21.8%) had mothers with one or more acute or chronic diseases, respectively. Of 22,475 mothers in the other CA control group, 8,999 (40.0%) and 3,793 (16.9%) were affected with one or more acute or chronic maternal diseases, respectively. The prevalence of these diseases was evaluated in the 2nd months of gestation, however, if diseases occurred in the 1st month and continued in the 2nd month were also included. Results: There was a potential recall bias between the NTD group and the normal control group, but not between the NTD group and the other CA control group. Conclusions: We suggest that maternal fever is a possible cause of neural-tube defects. Thus, these fevers should be treated with antipyretics during pregnancy. Among chronic maternal diseases, the possible association of migraine-headache, on the one hand and neural tube defects (particularly anencephaly) on the other hand cannot be excluded. © Springer-Verlag 2004.