The epidemiology of neural tube defects was reviewed, using data from two birth defects surveiliance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta Congenltai Defects Program, for 1970–1978 and 1968–1979, respectiveiy. After excluding cases with recognized causes, neural tube defects were divided into two major groups: “singles” and “multiples,” depending on the presence of associated major defects. Only singles, which accounted for the majority of cases, were shown to have the well-known epidemiologic characteristics of neural tube defects: marked predominance of females and whites, geographic variation with an east-to-west gradient, and decreasing rates over time. On the other hand, muflipies had no excess of females and occurred iess predominantiy in whites; moreover, their rates showed no geographic variation and ilttie or no downward trends over time. The presence of associated defects indicates that neural tube defects are epidemioiogicaiiy and probabiy etioiogicaiiy heterogeneous. It is suggested that anaiytlc studies of neurai tube defects may be more rewarding if they try to identIfy different risk factors associated with various subgroups. This approach to the study of birth defects may provide better clues to their etioiogy and pathogenesis.