As a result of the large difference between scattering mean free paths and absorption lengths in brain tissue, scattering dominates over absorption by water and intrinsic molecules in determining the attenuation factor for wavelengths between 350 nm and 1300 nm. We propose using longer wavelengths for two-photon excitation, specifically the 1300-nm region, in order to reduce the effect of scattering and thereby increase imaging depth. We present two photon fluorescence microscopy images of cortical vasculature in in vivo mouse brain beyond 1 mm. We also explore the capabilities of the 1300-nm excitation for third harmonic generation microscopy of red blood cells in in vivo mouse brain.© (2010) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.