The effects of exencephaly on cranial morphogenesis were studied at 10 to 12 days of gestation in the loop-tail (Lp) mutant mouse in which the hindbrain and spinal cord fail to close. At the level of the hindbrain, the otocysts became displaced ventrally in abnormal (Lp/Lp) embryos, and the everted neuroepithelium showed a diminished "luminal" reaction to the lectins WGA and Con A, as compared with normal embryos. Also, occasional clusters of rounded cells that resembled presumptive neural crest cells and that labeled with WGA, Con A, and anti-N-CAM were observed at the everted tips of the open neural folds. By 12 days' gestation, there was a loss of integrity in some areas of the neuroepithelium. However, despite the topographic and neuroepithelial distortions, normal differentiation of a roof plate-like neuroepithelium occurred at the ends of the everted neural folds. In addition, the mesenchyme showed normal condensations that labeled with WGA, Con A, and anti-N-CAM in the perinotochordal basicranium and periotic regions. Thus, in this mutant mouse model of neural dysraphism, some features of cranial morphogenesis and differentiation appear to be dependent on timely and proper closure of the cranial neural tube, whereas other aspects may proceed independently of neural closure.