A two-phase cultivation system was developed which will enable studies of streptomycete differentiation by molecular biological and global techniques such as transcriptomics and proteomics. The system is based on a solid phase formed by glass beads corresponding to particles in soil, clay, or sand natural habitats of streptomycetes. The beads are immersed in a liquid medium that allows easy modification or replacement of nutrients and growth factors as well as radioactive labeling of proteins. Scanning electron microscopy was used to analyze morphological differentiation of streptomycetes on glass beads and two-dimensional protein electrophoresis to demonstrate the potential of the system for analyses of protein synthesis profiles during the developmental program. This system facilitates studies of differentiation including expression and post-translation modifications of streptomycetes proteins, secondary metabolite biosynthesis, and morphological development.