Squid giant axons were photosensitized by dyes applied internally or externally in air saturated solutions and photochemically modified by visible light. For most dyes the modifications included an irreversible block of sodium channels, a destruction of inactivation in some of the unblocked channels, and a slowing of inactivation. Internal application was up to 100-fold more effective in blocking sodium channels than external application, suggesting a site of block nearer the internal surface. Rose Bengal sensitized channel block and destruction of inactivation when applied internally, but sensitized only channel block when applied externally. In contrast, externally applied Eosin Y sensitized a clear slowing of inactivation plus channel block. Beta-carotene, an effective agent for quenching photochemically generated excited singlet oxygen, inhibited most of the modification sensitized by internally applied Methylene blue but not by Rose Bengal or Merocyanine 540.