The role of increased cerebrospinal fluid pressure and morphogenetic brain expansion on midbrain wound healing was studied in chick embryos at stages 16-22. The embryos were divided into six groups as follows: group I (stages 16/17), group II (stages 18/19), group III (stages 20-22), group IV (stages 18/19), group V (stages 20-22) and group VI (stages 18/19). The mid-brains of embryos of groups I-III were wounded and the embryos re-incubated for varying periods up to 24 h. The neuroepithelial wounds of all group-I embryos healed completely within 24 h. However, complete healing was observed in only 25% of wounds in group II and 11.4% in group III by 24 h. To reduce cerebrospinal fluid pressure and thus slow down brain expansion, longitudinal wounds (about 0.8 mm long) were made in the hindbrain roof plate of group-IV and group-V embryos, and puncture wounds (0.1 mm in diameter) also in the hindbrain roof plate of group-VI embryos. This allowed cerebrospinal fluid to escape prior to wounding the midbrain. There was a significant increase in the proportion of group-IV and group-V embryos with completely healed midbrain neuroepithelial wounds (77.3% and 28.6% respectively). However, a comparison between groups II and VI embryos yielded no statistically significant difference in healing. Thus, increasing cerebrospinal fluid pressure and brain expansion adversely affect midbrain neuroepithelial wound healing.