The Ashkenazi Jewish population is unique in that DNA-based testing for multiple recessive disorders can be evaluated as a prototype for future prediction-prevention programs. Previously, multiple option screening in this population for Tay-Sachs disease (TSD), cystic fibrosis (CF), Gaucher disease(GD), and Canavan disease (CD) showed a high level of acceptance. Since molecular carrier detection is now feasible for Niemann-Pick disease type A(NPD), the program was expanded to determine the risks and benefits of carrier screening for NPD which is a less common, but severe neurodegenerative disease. In a study of 34 affected NPD type A chromosomes, three mutations in the acid sphingomyelinase gene (R496L, fsP330, L302P) were found to account for 94% of mutant alleles. To determine the population frequency of NPD alleles, 1224 Ashkenazi Jewish individuals with no family history of NPD were screened anonymously for the three mutations and 15 carriers were identified(1:82 carrier frequency). Couples were offered testing for TSD, CF, GD, CD, and NPD after receiving educational materials and attending a group genetic counseling session. Of the 497 Ashkenazi Jewish individuals who were offered testing, 97% selected all five disorders. The most important factor in accepting NPD testing was the severity of the disorder, while those who declined testing thought that their chance of being a carrier was small. Screenees uniformly chose testing to identify their risks. Acceptance was more highly correlated with disease severity than with disease frequency and attitudes toward terminating an affected fetus varied with disease severity and treatability. Thus, preliminary studies indicate that prenatal carrier testing for NPD has a high degree of acceptance in this population, but continued studies are necessary to evaluate strategies for the delivery of testing for five or more disorders as future technologic advances will make multiple disease testing a reproductive planning option for the general population.