AbstractThe effects of polyinosinic, polycytidylic acid [poly(I) · poly(C)] on the activation and RNA metabolism in murine peritoneal macrophages (MΦ) elicited by proteose‐peptone (pMΦ) was investigated. Poly(I) · poly(C) triggered the cytolytic activity of pMΦ and augmented their glucose oxidation. In contrast, a profound depression of [3H]uridine incorporation into RNA was observed in poly(I) · poly(C)‐activated pMΦ. The degree of depression of RNA labeling paralleled the dose of poly(I) · poly(C) used to activate the pMΦ and the expression of tumoricidal activity. This decrease in [3H]uridine incorporation into MΦ RNA could not be accounted for by decreased permeability of the activated MΦ to [3H]uridine, or by instability of the labeled RNA. Moreover, analysis of the specific activity of the intracellular uridine triphosphate (UTP) pool and studies on the labeling of MΦ RNA with [32P] orthophosphate indicated that the decreased RNA labeling was not due to changes in the specific activity of UTP. We concluded that poly(I) · poly(C)‐activated pMΦ exhibit a depressed rate of RNA synthesis. We suggest that the rate of RNA synthesis may be investigated as a potential new indicato