We studied the expression and possible functional role of chemokine receptors CXCR3, CXCR4 and CCR5 in normal human B lymphocytes. B cells from both peripheral blood and tonsils expressed high levels of CXCR4 but not the other chemokine receptors tested. CXCR4 ligand, stromal cell‐derived factor (SDF)‐1α, elicited a potent chemotactic response and induced a polarized motile phenotype in B cells, resulting in redistribution of the adhesion molecule ICAM‐3 to a posterior appendage of the cell, termed uropod, and of CXCR4 receptor to the leading edge of migrating B cells. Time‐lapse videomicroscopy studies revealed that SDF‐1α‐treated cells recruited additional bystander B cells through the uropod. SDF‐1α induced levels of cellular recruitment comparable to those elicited by polarization‐inducing anti‐ICAM‐3 monoclonal antibody, in an LFA‐1/ICAM‐1, −3‐dependent fashion. Moreover, this chemokine increased intracellular Ca²⁺ levels in B lymphocytes, and induced a rapid CXCR4 receptor down‐regulation on the cell surface membrane. These results provide new insight into the important biological role of SDF‐1α in physiological processes in which B cells participate, and suggest a key role for chemokines in normal B cell trafficking and recirculation.