Nuclear envelope breakdown was investigated during meiotic maturation of st
arfish oocytes. Fluorescent 70-kDa dextran entry, as monitored by confocal
microscopy, consists of two phases, a slow uniform increase and then a mass
ive wave. From quantitative analysis of the first phase of dextran entry, a
nd from imaging of green fluorescent protein chimeras, we conclude that nuc
lear pore disassembly begins several minutes before nuclear envelope breakd
own. The best fit for the second phase of entry is with a spreading disrupt
ion of the membrane permeability barrier determined by three-dimensional co
mputer simulations of diffusion. We propose a new model for the mechanism o
f nuclear envelope breakdown in which disassembly of the nuclear pores lead
s to a fenestration of the nuclear envelope double membrane.