We are investigating the 3D structure of biological macromolecular complexes using cryo-TEM techniques. We record TEM images of biological macromolecules (mainly proteins) embedded in amorphous ice and computationally reconstruct the 3D structure, either by tomography or single particle analysis. In tomography, projections of the object are obtained from various orientations by tilting the TEM stage. In single particle analysis, images of many particles, supposedly sharing one identical 3D structure, but randomly oriented in ice, are computationally aligned and merged into a 3D structure. We are also developing algorithms for image analysis and specimen preparation as well as data acquisition techniques. Our target biological macromolecules are cilia (group of T. Ishikawa), G-protein coupled receptors (group of G. Schertler and R. Benoit), microtubule binding proteins (group of M. Steinmetz) and membrane adenylyl cyclases (group of V. Korkhov).