A Zymate Laboratory Automation System (Zymark Corp.), previously set up for the automated synthesis of 16 alpha-[18F]fluoroestradiol-17 beta [Brodack et al. (1986a) J. Nucl. Med. 27, 714] has been modified for the production of several short-lived radiopharmaceuticals in a single hot cell. All manipulations and apparatus normally used in the syntheses of carbon-11 and fluorine-18-labeled radiopharmaceuticals have been incorporated into the robot system. This achievement permits facile modifications of existing procedures used by the robot in addition to the incorporation of new routines in a minimal amount of time. Currently, the Zymate robot is programmed for the routine production of 16 alpha-[18F]fluoroestradiol-17 beta (7-11% EOS in 80 min), N-(3-[18F]fluoropropyl)spiperone (15-18% EOS in 70 min), and [1-11C]butanol (11-15% EOS in 25 min). A fourth compound, 2-deoxy-2-[18F]fluoro-D-glucose, is also synthesized by the robot. The yields and synthesis times of the robot-produced compounds are comparable to those obtained during manual syntheses. This method of automation represents a flexible and versatile alternative for the routine production of radiopharmaceuticals used in PET studies.