The role of the microtubule-associated protein (MAP) tau in axon growth remains controversial. Antisense experiments have suggested that tau is required for axon outgrowth, whereas genetic knockout and immunodepletion studies have suggested that tau plays no role in this process. To investigate the role of tau in both neurite outgrowth and growth cone motility, we have used a different approach, the chromophore-assisted laser inactivation (CALI) of tau in chick dorsal root ganglion (DRG) neurons in culture. This approach generates an acute loss of tau function that is not subject to compensation by other MAPs. Inactivation of tau in whole DRG neurons (including cell body and neurites) reduced neurite number and length. Inactivation of tau within regions of growth cones using micro-scale CALI caused a decrease in neurite extension rate by approximately 2-fold. Surprisingly, it also caused a similar to 20% decrease in the lamellipodial size within the inactivation region, whereas the filopodial motility was not affected. These results suggest that tau is required in neurite outgrowth and that tau also functions in lamellipodial motility at the growth cone leading edge. Cell Moth. Cytoskeleton 43:232-242, 1999. (C) 1999 Wiley-liss, Inc.