Summary Cheilognathopalatoschisis (cleft lip, -maxilla, and -palate) is the second most frequent malformation in humans. The ontogenetic causes are mostly multifactorial. Some researchers have succeeded in lowering the frequency of occurrence of such clefts in children of predisposed women by giving the latter an applied symptomatic replacement therapy with multivitamin preparations or other substance classes during early pregnancy. However, the dosage of these substances was only anecdotal and their effect unspecific. Many research groups world-wide are conducting animal experiments in order to investigate the efficacy of vitamins and other substances as prophylactics. The experiments are usually conducted with laboratory rats and mice, and clefts are often induced by applying chemical noxa. The results of these trials, however, are controversial. Where some authors were able to prove protective effects of the vitamins or other substances they employed, others found evidence that such replacement therapy has no prophylactic effect. This paper provides insight into such studies with experimental animals, and compares their results.