Agents assigned to this level are associated with disease which may cause serious or lethal infection and for which preventive or therapeutic interventions may be available.

Aerosol is a common route of transmission for most RG3 agents (HIV is an exception). Transmission by the aerosol route increases the risk potential for these pathogens because aerosol-transmitted pathogens are more difficult to contain.

• Francisella tularensis
• Mycobacterium tuberculosis complex species (including M. bovis)
• Human immunodeficiency virus (HIV)

Personnel must typically wear respiratory protection and demonstrate proficiency in lab techniques that ensure personnel protection. Specific facility features designed to protect the surrounding environment are also required.