Abstract. A basic copolymer of ornithine and leucine (1:1) was shown to rapidly agglutinate, in the absence of serum, normal cells and cells transformed by viral and nonviral carcinogens. This agglutination was inhibited by addition of serum. In presence of serum, the same copolymer and those of ornithine and valine (1:1) and arginine and leucine (1: 1), produced a specific aggregation of simian virus 40 (SV40)-transformed cells cultured for about 24 hr after addition of the peptide. The rapid agglutination and SV40-specific aggregation could not be inhibited by a variety of individual amino acids or carbohydrates. The specific aggregation could be detected in mixtures of SV40-transformed and other cells, and it was not prevented by x-irradiating the cells with 4000 R. Aggregation of the SV40-transformed cells was inhibited by acidic polyamino acids provided these were added not later than about 5 hr after addition of the basic copolymer. The results indicate that the basic copolymer, in the presence of serum, produces a change in SV40-transformed cells, presumably in the surface membrane, that causes the cells to aggregate. In addition to the aggregation of cells transformed by SV40, cells transformed by adenovirus 12, which did not contain detectable SV40-specific nuclear tumor (T) antigen, were also aggregated by the basic copolymer in the presence of serum. This indicates that the ornithine,leucine copolymer is able to detect an SV40-like change in the surface membrane of cells transformed by adenovirus 12.The change in cellular regulatory mechanism that is produced by the transformation of normal cells by carcinogenic agents can be ascribed to a change in the cell-surface membrane.1 The use of chemicals with specific binding sites should be of value in elucidating the nature of this structural change. Results obtained with the carbohydrate-binding protein concanavalin A have indicated that binding sites for this protein exposed on the surface of transformed cells are in a cryptic form on normal cells.2 The exposure of other carbohydrate-containing sites on the surface membrane of transformed cells has also been suggested from agglutination experiments with a wheat germ glycoprotein3 and a soybean glycoprotein.4 The results of these studies have shown changes that were common to cells transformed by various types of carcinogens. The present studies with synthetic polyamino acids were undertaken to determine whether these compounds may be useful in further elucidating the difference between normal and transformed cells, and whether they could be used to detect membrane changes that may be specific to cells transformed by different carcinogenic agents.