SYNOPSIS. Experiments were designed to examine the nature of the response of Tetrahymena pyriformis to inhibitory levels of L‐serine when growing in defined media with carbohydrate as mono‐, or polysaccharide. Growth curves indicated that, when a polysaccharide is being utilized, inhibition by serine affects at least 2 different loci. At one locus, inhibition causes a marked increase in the growth lag, at the other a significant decrease in the maximum rate of growth. Since the inhibition was completely reversible by glucose supplementation, it is evident that the initial inhibition, expressed as increased lag time, is specifically related to uptake or metabolism of the polysaccharide, i.e., it precedes glucose in the metabolic sequence. The inhibition expressed as decreased rate of maximum growth appears to be due to interference at some stage in the glycolytic pathway. The results suggest that in metabolizing a polysaccharide, T. pyriformis utilizes 2 mechanisms simultaneously. One involves phagocytic ingestion of molecular dextrin followed by phosphorylytic cleavage whereby the energy of the glycosidic bond is utilized to form glucose‐1‐phosphate. The 2nd mechanism depends upon elaboration of extracellular hydrolytic enzymes to cleave the polysaccharide to glucose, which enters the glycolytic pathway via glucose‐6‐phosphate in the usual manner.