ABSTRACT The La Jolla Institute for Immunology (LJI) is a premier immunology research institute in the US whose 20 principal investigators are supported by ~$39 million in NIH grants and contracts. At LJI, we study the behavior of immune cells in diseases prominent in the US and around the world, including viral biology, type 1 diabetes, atherosclerosis, cancer, and inflammation. Nearly all of our scientists use imaging to visualize cellular interactions, signaling, and function with results published in Nature, Science, and other prominent journals. However, as our research aims evolve, and to progress further in the research projects listed in this application, we need a reliable and versatile super-resolution confocal microscope with multiscale imaging capability. The LJI Microscopy and Histology Core Facility is a dynamic, scientifically driven, multi-user resource with a remarkable potential for growth. The instrumentation in the LJI Microscopy Core Facility includes an aging Zeiss LSM 780 that is used by many NIH funded projects, with aims ranging from the investigation of matrix protein assembly in SARS-CoV-2, novel cell types in atherosclerosis, molecular pathways leading to Type 1 diabetes, and many others. This system is nearing the end of its useful lifetime and a replacement microscope is needed. Here, we seek support for purchasing an automated, state-of-the-art, super-resolution microscope that allows for multiscale, high-throughput investigation of mouse and human tissues. Dynamic biological processes can be probed thanks to innovative software, highly sensitive detectors, and unparalleled acquisition speed. After comparing instruments on the market from all major companies, it is clear that the Zeiss LSM 980 with Airyscan 2 system is the best suited for the needs of LJI investigators and collaborators, and if funded, it will undoubtedly have a significant impact on NIH-supported scientific progress.