1. 1. 53 strains of Neurospora crassa, representing 4 wild types and 40 mutant loci, were examined for accumulation of acid-soluble inorganic polyphosphate. When grown on a limited supply of growth factor, most of the mutants were found to accumulate polyphosphate, though the amounts varied widely. 2. 2. The time sequence of polyphosphate accumulation was studied in shaken cultures of the histidine-requiring strain, C-84. When growth ceased due to exhaustion of the amino acid, the RNA content of the mycelium dropped sharply. Concomitantly, acid-soluble polyphosphate accumulated; the levels of other phosphorus compounds, including the acid-insoluble polyphosphate, were not affected. 3. 3. By the use of 32P it was demonstrated that, in C-84, extensive degradation of RNA occurred upon exhaustion of the histidine. The phosphorus released from RNA was converted to polyphosphate and constituted a major source of phosphorus for polyphosphate accumulation. Similar observations were made with other mutant strains, though the details of the pattern of growth, RNA degradation and polyphosphate accumulation varied from strain to strain. 4. 4. Inhibition of the growth of Neurospora strains by withholding a macronutrient or by addition of a metabolic inhibitor did not, in general, induce either RNA degradation or polyphosphate accumulation. However, when mycelium was transferred to medium lacking the carbon source, sucrose, extensive degradation of RNA took place. Acid-soluble polyphosphate and inorganic orthophosphate accumulated under these conditions. 5. 5. Polyphosphate accumulation was inhibited by certain amino acid analogs. In C-84, the histidine analog 2-thiazolealanine was found to inhibit RNA degradation but had no effect on the accumulation of polyphosphate. 6. 6. The relationship of polyphosphate accumulation to the primary genetic block is discussed. The possible role of RNA degradation as the immediate cause of polyphosphate accumulation is considered.