The sporulating plasmodium of the slime mold Physarum polycephalum is an excellent system for studies on differentiation. Ample material maintained in axenic culture is available for biochemical studies; the changes are synchronous, distinct, and separate from growth; and the process may be easily initiated by starving a plasmodium and then exposing it to light. Studies reveal that sporulation is dependent on the synthesis of DNA prior to the period of illumination, on the continued synthesis of protein throughout the entire period, and on the synthesis of RNA until approx. 3 h after the end of the illumination period. Three hours after light exposure also marks the time at which processes associated with the early stages of sporulation attain a point of no return-a time at which the plasmodium is irreversibly committed to sporulate even though it is returned to a growth medium. © 1969.