Analyzing the infection of a host organism by parasites has remained a challenge because previous studies — conducted postmortem or in vitro — could not accurately demonstrate immunological reactions or the dynamics of cell invasion. Recently, scientists have been able to image the infection routes of parasites in a host in vivo with transgenic parasites expressing green or red fluorescent proteins. Volker Heussler of the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, and Christian Doerig of the University of Glasgow in the UK report on imaging techniques that elucidate host-parasite interactions. Wide-field and spinning-disk fluorescence microscopies have been employed to follow sporozoites in the skin and blood vessels of mice. Intravital microscopy has been used to track the infection routes of Plasmodium parasites. Observations at the cellular level have shown parasites to attach to blood vessels in the liver, glide along the endothelial cell layer and migrate through several cells before settling down in a final hepatocyte. The authors report the use of intravital microscopy to demonstrate the protrusion of infected cells toward blood vessels of the liver, thus confirming a hypothesis on the infection of red blood cells. Although intravital microscopy holds many advantages, the authors note several drawbacks to the technique. Excitation of the fluorescent proteins could damage the parasites or result in photobleaching. Laser-scanning multiphoton microscopy has lower energy and greater penetration; however, it has poor resolution and a low sampling speed not optimal for three-dimensional imaging. Heussler and Doerig expect intravital microscopy to further improve the study of immune responses against pathogens, particularly the interaction of infected cells with major organs such as the lungs and brain. They believe that this will open doors to drug discovery and vaccine development. (Trends in Parasitology, May 2006, pp. 192-195.)