We report here on the current state of our efforts in automated molecular microscopy. Our primary automated data acquisition software system, Leginon, has been completely redesigned over the past two years. The new distributed system has been developed using the Python programming language and is compatible with both Linux and Windows operating systems. The new flexible architecture was designed to allow for the development Of Customized data collection protocols, several of which are described here. The system has been used to acquire data for similar to 150 experiments and we have demonstrated the capacity for high throughput data acquisition by acquiring images of more than 100 000 particles in a single session at the microscope. (C) 2005 Elsevier Inc. All rights reserved.