Regulated on activation, normal T cell expressed and secreted (RANTES) serum concentrations were explored in a prospective observational study of haematological-malignancy patients undergoing chemotherapy. During systemic inflammatory response syndrome/sepsis or severe sepsis/septic shock mean concentrations were 3394 or 2939 pg/ml, respectively, significantly lower than those prior to fever (6031 pg/ml) (P < 0.01) or at bone-marrow recovery (6433 pg/ml, P < 0.001). Levels during febrile-bacteraemia were lower compared with febrile-non-bacteraemia (3022 pg/ml vs. 5111 pg/ml, respectively, P < 0.01). Sixty-three of 67 infection episodes resolved despite low RANTES concentrations, suggesting RANTES is not a prerequisite for recovering from most infection events. However, in four patients dying from septic shock associated with aspergillosis, candidosis, pneumonia or infectious colitis, RANTES concentrations were persistently and extremely low (1629 pg/ml), compared with four matched patients who recovered (6780 pg/ml). RANTES concentrations were highly correlated to platelet counts [median correlation coefficient 0.82 (inter-quartile range, 0.72-0.89)]. RANTES concentrations rose 4.5 d before platelet counts (P < 0.001), suggesting an additional extra-platelet source for RANTES. A nested mixed model regression analysis demonstrated that platelet level was the only independent variable associated with RANTES concentration (P < 0.001) among steroids, haematopoietic-colony-stimulating-factor, recombinant-human-interleukin-11, sepsis status, and neutropenia. A significant 'hypo-RANTES' serum environment occurs following chemotherapy, is driven by thrombocytopenia, but does not affect the ability of most patients to recover from infection.