T h e effects of different carbohydrates on cell-to-cell adhesion were examined in an aggregation assay, which consisted of swirling a suspension of cells and monitoring t h e loss of single cells with a Coulter Counter. Of t h e carbohydrates tested, only heparin and dextran sulfate induced cell aggregation. This effect occurred in freshly isolated mouse splenocytes and in cultured cells of lymphoid origin (P388, YAA-CI) but not in cell lines of fibroblastic origins (3T3, SV-3T3, BHK, and PY-BHK). Using t h e YAA-CI cell line for further study, we found that aggregation could be induced by relatively small amounts of heparin ( < I 0 pghl). Binding experiments with 3H-heparin showed that under normal physiological conditions each YAA-CI cell bound approximately 2 x lo6 molecules of heparin at saturation with a Kd of 3.5 x 10-7 M. This binding was blocked by both unlabelled heparin and dextran sulfate but not by other carbohydrates. When the pH of the medium was decreased, the heparininduced aggregation was inhibited, and the Kd of t h e 'H-heparin binding was increased. In a similar fashion, when the ionic strength of the medium was increased, heparin-induced aggregation was inhibited and the Kd of the interaction was increased. These results suggest that the aggregation is inversely related to the Kd of the interaction and that the binding of heparin to t h e cell surface is primarily of an ionic nature.